In New York City, advertising executive Roger Thornhill attends an informal business meeting at The Plaza hotel, where, intending to send his mother a wire, he summons a bellboy who has just paged George Kaplan. Across the room, two men, Valerian and Licht, believe Roger’s summons is acknowledgment that he is Kaplan and when Roger leaves the bar, forcibly take him to a waiting car and drive him to the private home of Lester Townsend in Glen Cove. There he is met by the suave Phillip Vandamm, who Roger believes is Townsend. Vandamm dismisses Roger’s claim that he is not Kaplan and urges him to reveal the information he wants. When Roger continues to deny being Kaplan, Vandamm's secretary, Leonard, forces Roger to drink an entire bottle of bourbon then places him behind the wheel of a car on a mountain road. Although completely befuddled by the liquor, Roger revives sufficiently to drive erratically down the hill until he is picked up by police. At court the next day, Roger and his lawyer describe his abduction and near murder, prompting the judge to order an investigation by county detectives. In the company of his mother and the detectives, Roger returns to the Townsend home but there is no sign of the kidnapping incident. A woman claiming to be Mrs. Townsend indicates Roger attended a party at the house the previous evening and reveals that Townsend is at the United Nations addressing the General Assembly. Roger and his mother return to The Plaza hotel in search of Kaplan. In Kaplan’s room, Roger finds a newspaper photograph of Vandamm who he still believes is Townsend, but is forced to flee when he realizes that Valerian and Licht have followed him. At the U.N., Roger requests to see Townsend, but is confused when the man he meets is not Vandamm. Perplexed, Roger is about to show Townsend the newspaper photo he found in Kaplan’s room when Townsend is struck in the back by a knife hurled by Valerian, who then escapes. As Townsend collapses into Roger’s arms, Roger grabs the knife in shock and is photographed by a nearby photo journalist. Horrified, Roger runs away. Later that day at the U. S. Intelligence Agency, a group of agents led by a man known as the Professor, discuss Townsend’s murder and Roger’s involvement. The Professor and his group are investigating Vandamm for selling government secrets and have created a fictitious agent named George Kaplan in hopes of forcing Vandamm into the open. When the agents wonder if they should intervene on Roger’s behalf, the Professor refuses, declaring that despite the danger to Roger, he is diverting attention from another agent working undercover with Vandamm. Meanwhile, Roger is labeled by newspapers as the U.N. murderer. Having learned that Kaplan has checked out of the hotel and is heading for Chicago, Roger sneaks aboard the Twentieth Century Limited. On board Roger meets an attractive blonde, Eve Kendall, who misdirects the police while he hides. Roger evades the conductors after the train gets underway, then visits the dining car where he is seated with Eve. Roger and Eve flirt with one another when she admits to tipping the waiter to seat Roger with her, but she also reveals to having seen the newspaper coverage accusing Roger of Townsend’s murder. When the train makes an unscheduled stop to allow two police detectives to board, Eve offers to hide Roger in her compartment overnight. Unknown to Roger, Eve is an associate of Vandamm, who is also onboard the train with Leonard. Upon arriving in Chicago the next morning, Roger disguises himself as a porter and escorts Eve off the train. Having concluded that Kaplan can lead him to Vandamm, Roger intends to meet Kaplan and Eve offers to make the arrangements so that Roger might maintain a low profile. After Roger changes clothes, he meets Eve who claims she has contacted Kaplan at the hotel and received explicit directions for their meeting. Roger follows Eve’s directions and by mid-afternoon waits for Kaplan alongside a deserted road in the middle of empty farm fields where a crop duster works in the distance. After several cars go by without stopping, the crop duster abruptly turns towards Roger and, to his amazement, makes several attacking passes at him. Roger seeks refuge in a corn field, but the plane dusts the field with a chemical powder, forcing Roger back into the open. Spotting an oncoming tanker truck, Roger desperately flags it down and stands directly in its path, forcing the tanker to stop. Still pursuing Roger, the plane swoops down at him and smashes into the tanker. When passers-by stop to gape at the scene, Roger steals a pickup and drives back to Kaplan’s Chicago hotel. There he is stunned to learn that Kaplan checked out before Eve’s purported conversation with him from the train station. Moments later, Roger spots Eve in the lobby and follows her to her room where she is startled to see him. Insisting that they cannot get involved with each other, Eve demands that Roger depart. Later, Roger follows Eve to an auction at an art gallery where she joins Vandamm and Leonard. Hurt over Eve’s betrayal, Roger angrily confronts them. Vandamm and Leonard scoff at Roger’s indignation, then bid on and win a small Mexican Tarascan Warrior figure, unaware of the Professor’s presence in the bidding audience. When Valerian and Leonard block the exits, Roger creates a scene, starting a fight in order to get himself arrested. The patrolmen report Roger’s seizure and are instructed to take him to the airport where he is met by the Professor, who explains about the fictitious Kaplan and the need to capture Vandamm with incriminating evidence before he departs the country from his ranch in South Dakota. Roger refuses the Professor’s request to continue posing as Kaplan until the Professor admits that Eve is their inside operative, and that she is now in grave danger of being exposed unless they can convince Vandamm of her loyalty. Upon arriving in Rapid City, Roger sets up a meeting with Vandamm at the cafeteria of the Mount Rushmore memorial. Just as he meets Vandamm, Roger stages an argument with Eve, climaxing in her shooting him with blanks. With Vandamm and Leonard convinced that Roger is critically wounded, the Professor takes Roger to meet Eve secretly and the two apologize to each other for their misunderstandings. Roger is dismayed, however, when Eve discloses that to maintain her cover she must accompany Vandamm out of the country that night. The Professor allows Eve to return to Vandamm and places the angered Roger in protective custody at a hospital. That night, Roger escapes and takes a cab to Vandamm’s ranch, beside which a small airplane runway is lit. Hiding near an open window, Roger overhears Leonard and Vandamm discussing the secret microfilm hidden in the warrior figure. Leonard then tells Vandamm that his long suspicion of Eve has been justified and demonstrates that Eve’s gun is filled with blanks. Deeply angered, Vandamm tells Leonard he will get rid of Eve during their flight that night. Alarmed, Roger climbs up the side of the house to warn Eve, but she leaves her room before he can talk to her. Writing a warning message on a matchbook bearing his initials, Roger then tosses it into the living room where Eve waits with Vandamm and Leonard as their private plane lands outside. After reading Roger’s note, Eve meets him in her room where he tells her of the microfilm and Vandamm’s plan to do away with her. When Eve joins Vandamm outside, Roger attempts to sneak out of the house but is held at gun point by the housekeeper. After escaping from the housekeeper, Roger steals Valerian’s car and races to retrieve Eve, who has snatched the warrior figure and darted away from Vandamm. Stopped by a locked gate, Roger and Eve proceed on foot, followed by Valerian and Leonard. Realizing they are trapped on top of Mount Rushmore, Roger and Eve start down the monument, but Roger is attacked by Valerian and Eve tussles with Leonard. After Roger hurls Valerian off the mountain, Leonard takes the figure and pushes Eve down the cliff where Roger comes to her aid as she dangles perilously on the edge of the monument. As Leonard menaces the couple, the Professor and his men come to the rescue, killing Leonard and arresting Vandamm in the process. Roger and Eve return to New York as man and wife, sentimentally taking the train.