Roy Scheider as Dr. Heywood Floyd

John Lithgow as Dr. Walter Curnow

Helen Mirren as Tanya Kirbuk

Bob Balaban as Dr. R. Chandra

Keir Dullea as Dr. David Bowman

Douglas Rain as HAL 9000 (voice)

Madolyn Smith Osborne as Caroline Floyd

Savely Kramarov as Dr. Vladimir Rudenko

Taliesin Jaffe as Christopher Floyd

James McEachin as Victor Milson

Mary Jo Deschanel as Betty Fernandez

Ilya Baskin as Maxim Brailovsky

Dana Elcar as Dimitri Moisevitch

Oleg Rudnik as Dr. Vasili Orlov

Natasha Shneider as Irina Yakunina

Vladimir Skomarovsky as Yuri Svetlanov

Victor Steinbach as Nikolaj Ternovsky

Candice Bergen as SAL 9000 (voice)

Gene McGarr as Commercial Announcer

Herta Ware as Jessie Bowman

Jan Tříska as Alexander Kovalev

Larry Carroll as Anchorman on TV

Cheryl Carter as Nurse

Ron Recasner as Hospital Neurosurgeon

Robert Lesser as Dr. Hirsch

Delana Michaels as Commercial Announcer

Arthur C. Clarke as Man on Park Bench (uncredited)