Nicotine intake is associated with lower body weight in both women and men. Despite its energy content, alcohol consumption is also associated with lower body weight in women but not in men. Each drug may reduce weight by acutely increasing thermogenesis. During four sessions, nicotine (20 micrograms/kg per dosing) or placebo was given to male and female smokers (n = 9 each) via measured-dose nasal spray every 30 min for 2 h after consumption of diet tonic water with or without alcohol (0.5 g/kg). Each nicotine/placebo dosing was followed by assessment of energy expenditure by indirect calorimetry. Alcohol alone induced no significant effect in men or women, whereas nicotine alone and combined with alcohol induced a significant thermogenic effect in men but not women. These results are consistent with other research suggesting a reduced thermogenic responsiveness to drugs in women and indicate that nicotine must act via appetite suppression to reduce body weight in women. Similarly, these findings do not support the notion that alcohol is inversely related to body weight in women because of excessive acute thermogenesis.