The interactive effects of caffeine and cigarette smoking were studied in fifteen subjects. Four experimental sessions presented either decaffeinated coffee or caffeinated coffee (containing 150 mg caffeine base), followed 20 min later by a smoking or nonsmoking period (20 min duration). Puffing behavior and end-expired air carbon monoxide concentrations were measured to estimate smoke intake. Subjective reports of arousal and tension, and physiologic measures of heart rate and blood pressure were collected. Subjective arousal showed a highly significant antagonistic interaction between caffeine and smoking; smoking blocked the subjective stimulant effects of caffeine. The only cardiovascular effect noted was an increase in heart rate after smoking. Caffeine did not significantly influence puffing behavior; however, the increase in end-expired carbon monoxide concentration after smoking was greater in the caffeine condition, suggesting subjects inhaled more smoke after caffeinated than decaffeinated coffee.