The effects of oral pentobarbital on cigarette smoking and subjective response were determined in 5 adult men with histories of alcoholism and cigarette-smoking habits. Subjects resided in a residential research unit for the 6-wk study and were individually tested 5 days/wk in rooms equipped for automatic monitoring of cigarette-smoking behavior. Each subject was tested with placebo, 1 dose level of ethanol (either 89 or 134 g absolute ethanol), and each of 3 pentobarbital doses (200-900 mg), in at least 4 randomized block sequences. Ethanol induced increases in puffs and other smoking measures in all subjects. Pentobarbital increased smoking in 2 subjects, whereas it did not induce change or suppress smoking in the other subjects. Both pentobarbital and ethanol increased scores on scales of the Addiction Research Center Inventory and other self-report measures. Apparently the effects of pentobarbital on smoking differ from those of ethanol, and the effects of both drugs on smoking may depend on previous experience of the subject in the use of those drugs.