- 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 interpreta a Howard Biggers en la serie.
Ray Walston interpreta a Howard Pratt en la serie.
Jack Kruschen interpreta a Gunther Starr en la serie.
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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