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The Interaction of caffeine with pentobarbital taken for its hypnotic effect was studied in 42 medical and surgical patients. Each patient received the following medications orally: a lactose placebo; 250 mg caffeine; 100 mg pentobarbital; and 250 mg caffeine plus 100 mg pentobarbital. Hypnotic effects were determined by patient evaluation of sleep. Caffeine had an adverse effect on sleep, whereas pentobarbital was an effective hypnotic. Together, their effects appeared additive, and the 250 mg caffeine plus 100 mg pentobarbital combination was not distinguishable from the placebo.