Although this episode was the last of season three to air, it was actually the first episode shot under Jonathan Miller's producership, and he purposely interpreted it in a manner divergent from most theatrical productions. Whereas the love between Antony and Cleopatra is usually seen in a very heightened manner, as a grand passion, Miller saw it as a love between two people well past their prime who are both on a "downhill slide, each scrambling to maintain a foothold." He compared Antony to a football player who had waited several seasons too long to retire, and Cleopatra to a "treacherous slut.
When shooting the scene with the snake, actress Jane Lapotaire, who was afraid of snakes even prior to the shoot, became quite panicked when the snake suddenly slithered down the back of her dress.
Jonathan Miller used Paolo Veronese's The Family of Darius before Alexander as a major influence in his visual design of this episode, as it mixes both classical and Renaissance costumes in a single image.
This is one of only two episodes in which original Shakespearean text was substituted with additional material (the other was Love's Labour's Lost (1985)). Controversially, Jonathan Miller and his script editor David Snodin cut Act 3, Scene 10 and replaced it with the description of the Battle of Actium from Plutarch's Parallel Lives, which is delivered as an onscreen legend overlaying a painting of the battle.