Epidemiological, clinical, and laboratory evidence has shown a positive correlation between cigarette smoking and ethanol use, and previous studies suggest some commonality in the neural pathways mediating effects of nicotine and ethanol. In this study, the subjective and behavioral interactions among nicotine, ethanol, and the nicotinic antagonist mecamylamine were investigated. The main objectives were to determine how the rewarding effects of nicotine might be modified by ethanol, and to compare the effects of ethanol with those of a nicotinic antagonist (mecamylamine). A total of 48 smokers who regularly consumed alcoholic beverages participated in four laboratory sessions presenting a 2 (nicotine vs. denicotinized cigarette smoke)x2 (10 mg oral mecamylamine hydrochloride vs. placebo)x2 (ethanol.5 g/kg vs. placebo) design, with ethanol as a between-subjects factor. Dependent measures included blood alcohol concentration (BAC), as assessed by breath alcohol detector; subjective drug effects; and rate of ad lib smoking during a 2-hr period. Results showed that peak BAC averaged.03 g/dl in the ethanol condition. Ethanol potentiated some of the subjective rewarding effects of nicotine, including smoking satisfaction, stimulant as well as calming effects, and relief of craving for cigarettes. During the ad lib smoking period, mecamylamine decreased satisfaction associated with the nicotine-containing cigarettes; mecamylamine also induced smoking but only in the placebo ethanol condition. These results highlight the potent interaction between ethanol and nicotinic systems, and suggest that ethanol can potentiate the rewarding effects of nicotine as well as offset some of the effects of a nicotinic antagonist.