During filming, Karl Malden's London hotel room was burgled and his cash was stolen, but his travellers' cheques were left untouched. The incident inspired him to become the spokesman for American Express travellers' cheques in a long-running series of commercials with the slogan "Don't leave home without them".
André De Toth was originally slated by producer Harry Salzman to helm "Billion Dollar Brain", but when the director broke his neck in a skiing accident, he recommended Ken Russell to replace him based on the latter's creative TV work. Russell was contractually obligated to direct the film. He did not want to do it, but according to him "it was shoved down my throat". De Toth reportedly did some direction but refused to take credit on a picture signed by another.
The movie contains several references to the work of director Sergei M. Eisenstein. Most notably the ice battle scene from Alexander Nevsky (1938), the red flag (seen flying over Riga, Eisenstein's birthplace) and the wounded nurse (the frozen Kaarna) from Battleship Potemkin (1925).
The three main actors have all won Academy Awards for Best Supporting Actor, Michael Caine for Hannah and Her Sisters (1986) and The Cider House Rules (1999), Karl Malden for A Streetcar Named Desire (1951) and Eg Begley for Sweet Bird of Youth (1962). (The latter two being in adaptations of Tennessee Williams' plays.) In addition, Michael Caine was nominated four more times for Best Leading Actor and Karl Malden once more for Best Supporting Actor (for On the Waterfront (1954)). Also, Oscar Homolka earned a nomination for Best Supporting Actor for I Remember Mama (1948). In total, there are four wins and eight nominations among the cast.