The series was sponsored by Drene Shampoo, and the announcer was Tobe Reed. Drene Time usually opened with Langford singing a big band-style arrangement. Then Ameche and Langford would slip into routine comedy, often aided by co-star Danny Thomas, in routines involving Ameche's frustration that Thomas seemed more interested in modern technology and discoveries than in women.
After another musical number and a commercial spot for Drene Shampoo, Ameche and Langford appeared as the Bickersons for the final 15 minutes of the show. The Bickersons segment, at that time, was titled, "The Honeymoon's Over."
An early audition show of July 31, 1946 featured a different cast: Don Ameche, guest Sylvia Sidney, announcer Truman Bradley, Joseph Lilley and His Orchestra, Pinky Lee, Jim Backus, the Swing Choir, Jonelle James, Earle Ross and announcer Marvin Miller.