LAPD Detective Sergeant Walter Brown (Charles McGraw) and his partner are assigned to protect the widow of a mob boss, Mrs. Frankie Neall (Marie Windsor), as she travels by train from Chicago to Los Angeles to testify before a grand jury. She also carries with her a list of bribes that belonged to her murdered husband. The mob hit men don't know what she looks like. On the way to pick her up, Brown bets his partner and friend, Sergeant Gus Forbes (Don Beddoe), what she'll look like: "She's the sixty-cent special. Cheap. Flashy. Strictly poison under the gravy."

As the detectives and Ms. Neall leave her apartment, a mob hit man named Densel (Peter Virgo) crosses their path. Forbes is shot dead, but Densel, though wounded by Brown, escapes. At the train station, Brown discovers that he has been followed by gangster Joseph Kemp (David Clarke). Kemp identifies Brown as the detective even before they board the train. Each knows the other is a mortal enemy. With the help of a conductor, Kemp enters Brown's room while Brown is there, under the pretext that he is looking for lost luggage. Meanwhile, an overweight man confronts Brown in front of other passengers to ask why Brown occupies a two-room compartment, while he is in the upper berth of one section.

Kemp tries to open the door to the adjoining compartment, where Mrs. Neall is hiding, but Brown tells the conductor that the room is empty, and Kemp and the conductor leave. Brown knows that Kemp will return to Mrs. Neall's room, so he hides Mrs. Neall in the ladies' room with all her luggage, and goes to the dining car to let Kemp know that the room is unguarded. Kemp then returns and searches both rooms, finding nothing. After Kemp returns to the dining car, Brown leaves the dining car to escort Mrs. Neall back to her room. Later, mobster Vincent Yost (Peter Brocco) meets Brown and tries unsuccessfully to bribe him to finger Mrs. Neall and leave her, appealing to both his greed and his fear (Brown tells Yost that he is under arrest for bribery, but Brown is out of his jurisdiction, so he has no authority to arrest him). He even suggests that Brown might use the bribe to help the family of his murdered partner, Gus Forbes.

Brown's relationship with Ms. Neall is caustic. She is a vile, profane brunette, who flirts with him while expressing doubts about his integrity and his commitment to protect her. She doesn't seem to care that Brown's partner has been murdered. On the train, she insists on playing records on her portable record player and endangers them both, which infuriates Brown. By chance, Brown strikes up a friendship with an attractive blonde train passenger he meets, Ann Sinclair (Jacqueline White), and her spoiled and overly observant young son Tommy (Gordon Gebert). When Kemp sees Brown with her, he mistakes Sinclair for his target. After Brown beats him in a fight and interrogates him, the cop learns of the mistake. Brown again attempts an arrest without stopping