The subjective and physiological effects of intravenously administered cocaine and nicotine were compared in 10 cigarette-smoking cocaine abusers. Subjects abstained from smoking at least 8 h before each session. Under double blind conditions, subjects received placebo, cocaine (10, 20, and 40 mg/70 mg), or nicotine (0.75, 1.5, 3.0 mg/70 kg) in mixed order. Physiological and subjective data were collected before and repeatedly after each intravenous drug administration. Subjects also completed a drug versus money multiple-choice procedure in which they chose between that day's drug and 44 monetary values. Both drugs increased blood pressure and heart rate and decreased skin temperature. Nicotine showed a more rapid onset of subjective effects than cocaine. Overall, although both cocaine and nicotine increased subjective ratings of "drug effect", "rush", "good effects", "liking", "high", and "stimulated", only nicotine increased ratings of "bad effects" and "jittery". Although the highest nicotine dose produced greater effects than the highest cocaine dose on most subjective measures, the highest cocaine dose produced somewhat greater ratings of drug liking. At doses that produced comparable ratings of drug effect (40 mg/70 kg cocaine versus 1.5 mg/70 kg nicotine), cocaine produced significantly greater good effects, whereas nicotine produced greater bad effects. All three cocaine doses and the intermediate and high nicotine doses were frequently categorized as producing effects similar to those of cocaine or amphetamine. The drug versus money measure showed that the highest cocaine dose was worth twice as much as the highest nicotine dose. Thus, intravenous cocaine and nicotine can be differentiated by their subjective and reinforcing effects.