Despite the fact that tobacco and marihuana are often used together, relatively little is known about the effects of this combination. In order to investigate the effects of the principal psychoactive component in tobacco smoke, nicotine, on marihuana-induced intoxication, we conducted a double blind, cross-over experiment using nicotine transdermal patches. Ten male and 10 female participants received either placebo or a 21 mg transdermal nicotine patch 4 h before smoking one of two marihuana cigarettes (1.99 or 3.51% delta-9-tetrahydrocannabinol (Δ 9 THC) content). Measurements of physiological activity (heart rate, blood pressure, and skin temperature) and subjective effects (self-reports of drug effects on visual analog scales (VAS) and the Addiction Research Center Inventory (ARCI)) were made periodically before and for 3 h after smoking. Nicotine pre-treatment enhanced several responses to marihuana, in particular, heart rate, reports of “stimulated” on the visual analog scales, and scores on the Amphetamine scale of the ARCI. Male participants reported a more pronounced effect of marihuana that persisted longer than that of the female participants. Compared to the male participants, female participants experienced an attenuated response to marihuana and were less affected by the drug combination. The results of this study show that nicotine can have an important influence on the subjective and physiological effects of smoked marihuana. These effects have implications for the safety and efficacy of marihuana smokers who are self-medicating with the nicotine transdermal patch to manage their tobacco dependence.