The hypothesized role of the beta-carboline norharman in processes of drug dependence forms the basis for several studies on plasma levels of norharman among substance-using populations, particularly among alcoholics and smokers. However, it is not clear whether norharman is implicated in processes of dependence to both substances, or only to tobacco smoke. In the present study plasma concentrations of norharman were measured among four groups of participants regarding heavy smokers who do or do not drink alcohol excessively and nonsmokers who do or do not drink alcohol excessively. All measurements were conducted on three different days with an interval of 2 months in between and at three times during the day to account for possible circadian or seasonal variations. Results showed that elevated plasma levels of norharman appear only in heavy smokers regardless of their drinking profile. The norharman plasma levels of nonsmoking excessive drinkers showed a similar pattern to that of the control group. The findings indicate that elevated plasma levels of norharman are due to heavy smoking and not to excessive drinking.