An extensive literature documents a close association between cigarette and alcohol use. The joint pharmacological effects of alcohol and nicotine on smoking and drinking motivation may help explain this relationship. This experiment was designed to test the separate and combined pharmacological effects of nicotine and a low dose of alcohol (equivalent to 1-2 standard drinks) on substance use motivation using a double-blind and fully crossed within-subjects design. Participants (N = 87) with a wide range of smoking and drinking patterns completed 4 counterbalanced experimental sessions during which they consumed an alcohol (male: 0.3g/kg; female: 0.27g/kg) or placebo beverage and smoked a nicotine (.6 mg) or placebo cigarette. Outcome measures assessed the impact of drug administration (alcohol or nicotine) on craving to smoke, craving to drink, affect, and liking of the beverage and cigarette. Results indicated that combined administration produced higher cravings to smoke for the entire sample, as well as higher cravings to drink among women and lighter drinkers. Heavier users of either alcohol or cigarettes also exhibited enhanced sensitivity to the effects of either drug in isolation. Separate, but not interactive, effects of alcohol and nicotine on mood were observed as well as both same-drug and cross-drug effects on beverage and cigarette liking. Together, these findings support the notion that the interactive pharmacological effects of nicotine and low doses of alcohol play an important role in motivating contemporaneous use and suggest roles for cross-reinforcement and cross-tolerance in the development and maintenance of alcohol and nicotine use and dependence.