The thermic effect of cigarette smoking is dampened by the thermic effect of a meal, but potentiated by the thermic effect of exercise. The impact of the combined influences of caffeine and cigarette smoking is unknown. We examined the 3-h thermic response to smoking four 0.8 mg nicotine cigarettes, ingesting 200 mg of caffeine, or both, in ten fasted healthy men. Smoking four 0.8 mg nicotine cigarettes increased resting energy expenditure (REE) by 3.3% over a 3 h measurement period. Consumption of 200 mg of caffeine in the fasted condition increased REE of the smokers by 4.8% over 3 hours. Smoking four 0.8 mg cigarettes and ingesting 200 mg of caffeine significantly increased REE by 7.5% during the 3 h measurement period. At times early in the observation period, the combined thermic effect of cigarettes and caffeine was more than additive, but the effect was short-lived. A control group of nonsmokers was studied comparing REE following placebo or 200 mg of caffeine. Caffeine increased REE in the non-smoking controls 6.7%. This was not significantly different from results obtained on smokers. Fasted and non-smoking (baseline) REE was similar in smokers and non-smoking control subjects. It was concluded that the effects of caffeine on REE are additive.