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In 1919, Terrance and Molly Donahue, a husband-and-wife vaudeville team known as The Donahues, pursue both success and a stable family life, and as the years pass, their act becomes The Five Donahues with the addition of their children, Steve, Katy and Tim. Worried that the children will suffer from their nomadic lifestyle, Molly persuades Tim to send them to a Catholic boarding school, but the youngsters, missing both their parents and the thrill of performing, continually try to run away. Comforted by Father Dineen's assurances that the children are better off with them, Terry and Molly buy a home in New Jersey for their brood. When the Depression hits, however, Terry and Molly are forced to take whatever jobs they can find, including singing for radio advertisements and working at a carnival. Eventually, movie theaters come to their rescue by providing live stage entertainment before showings, and the Donahues are performing once again. In 1937, Tim graduates from high school, and the act again becomes The Five Donahues, with Katy concentrating on dancing, Steve demonstrating an admirable singing voice, and Tim being an all-around performer like his father. The family is a success and soon are performing in a show at the Hippodrome Theatre in New York, where their extravagent performance of "Alexander's Ragtime Band" thrills the audience. One night after a show, a worried Molly and Tim return home alone while Katy goes out on a date, Steve takes a walk and the womanizing Tim goes out with an older chorus girl. Katy and Tim both wind up at Gallagher's, where Tim teases hatcheck girl Victoria Hoffman about the unnatural elocution her singing teacher has instructed her to practice. Vicky forgets Tim's wisecracks when Eddie, her agent, informs her that he has persuaded famed producer Lew Harris to visit the club. With the help of her co-workers, Vicky gets onstage and impresses Lew and Tim with her singing. Backstage, Vicky learns that Tim is one of the well-known Donahues, but quickly dismisses him in order to talk business with Harris. Back at the Donahue home, Molly and Terry welcome Katy and then Steve, who informs his family that he wants to become a priest. Terry is distraught over his son's decision, but their discussion is interrupted by the appearance of Tim, who got drunk after leaving Vicky. Later, having accepted Steve's choice, the family throws him a farewell party, and The Four Donahues accept an engagement in Miami. Tim is thrilled to find that Vicky, now known as Vicky Parker, is also appearing there, and gives his approval for her to perform a number that Molly had planned for the Donahues to do. Vicky is a sensation and Tim falls in love with her, although she gently shrugs off his proposals so that she can focus on her career. Molly, still irate that Vicky "stole" her song, is further irritated upon learning that Harris is staging a Broadway revue around Vicky, and that Vicky wants Tim and Katy to join her. Realizing what a great opportunity it is, Terry persuades Molly to let the kids go, and soon Molly and Terry are performing on their own again while Tim and Katy rehearse with Vicky in New York. Katy begins dating lyricist Charlie Gibbs, and after Steve is ordained, he agrees to perform their wedding ceremony. Tim continues dating Vicky, but one night, she postpones their dinner in order to discuss a costume change with Harris. Vicky loses track of time and stands Tim up, and Tim, mistakenly assuming that Vicky is having an affair with Harris, gets drunk and becomes involved in a car accident. Molly and Terry learn of the accident just before the show is to open, and while Molly, who has been rehearsing with Katy, goes on in Tim's place, Terry goes to the hospital. There, he discovers his son only slightly injured but greatly embittered, and when Terry lectures him on his responsibilities, Tim's snide reply prompts Terry to slap him and storm out. The next day, Molly and Terry go to the hospital to pick up Terry but discover that he has vanished, leaving a note apologizing for his behavior. While Molly continues to perform in the show, the Donahues hire private detectives to search for Tim, and scour the clubs and bars of New York looking for him. After almost a year, Steve joins the Army as a chaplain, while Molly still blames Vicky for Tim's disappearance. Terry shows no interest when Molly tells him that the Donahues are being sought for a benefit performance at the Hippodrome before it is closed, and instead disappears to search for Tim. Weeks later, on the day of the benefit, Katy, who is close friends with Vicky, arranges for her to share a dressing room with Molly, and Vicky convinces Molly of her genuine love for Tim. Finally forgiving Vicky, Molly is also comforted by the arrival of Steve, who tells her not to lose hope that Tim and Terry will come home. Steve and Katy watch from the wings as Molly wows the crowd with a rendition of "There's No Business Like Show Business," then gesture wildly to her as Tim, wearing a Navy uniform, appears beside them. Molly rushes to embrace her son, who tells her that he had to work things out for himself, and the family is complete when Terry joins them. Thrilled to be reunited, The Five Donahues, with Vicky holding Tim's hand, go onstage and happily reprise their version of "Alexander's Ragtime Band."