Nicotine from the alkaline smoke of cigars is absorbed through the buccal mucosa, but such absorption from the more acidic smoke of American cigarettes has not been reported. Forty-one male and 52 female smokers were studied under normal ventilation and smoking conditions, and under high ventilation and controlled smoking conditions that restricted intake to the mouth only, with no inhalation. The major finding is that there is virtually no intake of nicotine through the buccal mucosa while smoking American cigarettes. Confirming prior reports, plasma nicotine and expired CO levels showed no correlation with the analytical yields of nicotine and CO of the cigarettes smoked. Fifteen nonsmokers (7 male, 8 female) participated in this study as controls. Data from these subjects provided additional information regarding absorption of nicotine and carbon monoxide during passive smoking. Within the highly ventilated environment, there was no significant change of CO and nicotine levels of nonsmokers. However, within the normally ventilated environment, there was minimal increase in both substances, statistically significant only for nicotine. These results suggest that nicotine may be a better indicator of exposure to second-hand smoke than carbon monoxide.