- Bill Dana - Salvatore Mercadonte
- Don Ameche - Dr. Norman Marsh
- Diana Muldaur - Paulette Sherman
- Edward Mulhare - Myles Prescott
- Dana Andrews - Lewis Marshall
- Orson Bean - Warren Wright
- Jim Backus - Howard Biggers
- George Maharis - Dr. Anthony Bender
- Dean Stockwell - Cliff Waddell
- Clu Gulager - Father Terrence Devlin
- Polly Bergen - Dina Carroll-Winer
- Donald O'Connor - Kenny Freeman
- James Shigeta - Stephen Yang
- Jack Kruschen - Gunther Starr
- John Hillerman - Simon Brimmer
- Michael Pataki - Al Russo
- Peter Hobbs - Medical Examiner
- Edward Andrews - Spencer Lockridge
- Rhonda Fleming - Laura Lockridge
- Julie Sommars - Emmy Reinhart
- Julie Adams - Jennifer Packer
- William Demarest - Alexander 'Pop' Denny
- George Burns - Sam Packer
- John Dennis - Tolson
- David Hedison - Roger Woods
- Ed McMahon - Lamont Franklin
- Dick Van Patten - Billy Geeter
- Ann Reinking - Lorelie Farnsworth
- Art Balinger - Newscaster (uncredited)
- Noah Beery Jr. - Lionel Briggs
- Carole Cook - Gossip Columnist
- Don DeFore - Dave Pierce
- Troy Donahue - Gilbert Mallory
- Paul Fix - Capt. Benjamin Blake
- Jack Murdock - Al Garvin
- James B. Sikking - Mike Hewitt
- Jack De Mave - Sonny North (uncredited)
- Joan Collins - Lady Daisy Frawley
- Barbara Rush - Emma Zelman
- Barbara Rush - Claire Mallory
- David Doyle - Donald Becker
- Farley Granger - Paul Quincy
- Charles Robinson - Lewis Halliday
- Ray Walston - Howard Pratt
- George Wyner - Joe Kemmelman
- Joseph V. Perry - Rawson
- William Lanteau - Avery Dickson
- Thayer David - Marcus Halliday (uncredited)
- Herb Edelman - Taxi Driver
- Herb Edelman - Max Sheldon
- Victor Buono - Dr. Friedland
- Vera Miles - Celeste Wakefield
- Forrest Tucker - Clint McGraw
- Woodrow Parfrey - Dr. Saltzman
- Diana Chesney - Edna, the Maid
- Dick Cherney - Auction Guest (uncredited)
- Bob Crane - Jerry Crabtree
- Carolyn Jones - Rita Radcliffe
- Juliet Mills - Florence Ames
- Arch Johnson - The Commissioner
- Arch Johnson - Deputy Commissioner Hayes
- Anne Francis - Nurse Evelyn Chandler
- Jack Kelly - Attorney J. T. Latimer
- Craig Stevens - Jonathan Kendrick
- Jimmy Lydon - Radio Actor
- Basil Hoffman - Technical Print Man, Harry
- Don Diamond - Police Officer (uncredited)
- Bob Harks - Wrestling Match Spectator (uncredited)
- Bill Quinn - Minister, J. P. Dell
- Robert Hogan - Gordon Wilde
- Robert F. Simon - Eben Wright
- Jerry Fogel - Deputy Ralph Brown
- Lynda Day George - Alma Van Dine
- Tom Bosley - Bud Armstrong
- Herbie Faye - Moe Fletcher
- Sandy Ward - Guard, Harry
- Ken Berry - DJ Paul 'Buddy' Parker
- Michael Callan - Gary Swift
- Norman Fell - Errol Keyes
- Albert Salmi - Herbie Morrow
- Rudy Vallee - Alvin Winer
- Dori Brenner - Laura Schramm
- Vince Howard - Charlie the bartender
- Richard Levinson
- William Link
Dean Stockwell interpreta a Cliff Waddell en la serie.
Jim Backus hace el papel de Howard Biggers.
Ray Walston interpreta a Howard Pratt en la serie.
Jack Kruschen hace el papel de Gunther Starr.
Jim Hutton hace el papel de Ellery Queen.
David Wayne hace el papel de Inspector Richard Queen.
Tom Reese interpreta a Sgt. Thomas Velie en la serie.
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