Ethanol and tobacco consumption are commonly associated. Both are risk factors for adverse cardiovascular events. To better understand the interactions, the influence of oral ethanol pretreatment (0.5 or 1.0 gm/kg over 60 minutes) on cardiovascular responses to and disposition kinetics of intravenous nicotine was studied in healthy volunteers. Ethanol increased heart rate, systolic blood pressure, and pressure-rate product in a dose-related manner. Nicotine had additive effects on heart rate and pressure-rate product. It also decreased skin temperature, reflecting cutaneous vasoconstriction, but this effect was antagonized by ethanol. Ethanol did not affect metabolic clearance but increased CLR of nicotine by 25%. Additive cardiovascular effects of ethanol and nicotine could contribute to arrhythmias and sudden death in patients with coronary heart disease. It is unlikely that an effect of ethanol on nicotine metabolism is responsible for increased cigarette smoking while drinking ethanol.