Nicotine and alcohol are often consumed together and smokers are more likely than non-smokers to drink alcohol. In spite of the high prevalence of the combined use of alcohol and nicotine, only a few laboratory studies have examined the effects of this drug combination in humans. The present study was conducted to further investigate the nature of nicotine/alcohol interactions by examining whether nicotine pretreatment via a transdermal patch (placebo or 21 mg) alters the subjective and physiologic effects of acute ethanol (0.4 and 0.7 g/kg) administration. Twelve male smokers who drank alcohol on an occasional basis provided informed consent to participate in the study. Subjective reports of feeling drunk, feeling ethanol's effects and ethanol-induced euphoria were increased by nicotine pretreatment. In addition, reports of desire to smoke a tobacco cigarette were significantly elevated after ethanol administration and were most pronounced during the active nicotine conditions. Heart rate was elevated by nicotine and ethanol-induced increases in heart rate were enhanced by nicotine pretreatment. The time to peak ethanol concentration was faster in the nicotine-patch condition and this paralleled the more rapid detection of ethanol effects after drinking the low-dose beverage. These findings suggest that nicotine enhances some of the positive subjective effects of acute ethanol and may help explain the high prevalence of the combined use of these two drugs.