The effects of mecamylamine (placebo, 5.0, 10.0, and 20.0 mg) on subjective and physiologic responses to IV nicotine (placebo, 0.75, 1.5, and 3.0 mg) were evaluated in seven healthy male volunteer cigarette smokers. Subjective and physiologic drug responses were collected 15 minutes prior to mecamylamine and at 10 and 45 minutes post-injection. Paired comparisons indicated that pleasurable effects reported after 0.75 mg of nicotine and aversive effects reported after 3.0 mg of nicotine both were blunted by mecamylamine. Mecamylamine attenuated both the dose-related decrease in tobacco craving following 3.0 mg of nicotine and nicotine-induced tachycardia. By blocking both positive and negative effects of IV nicotine, mecamylamine may be a useful adjunct to nicotine replacement treatment, possibly resulting in fewer side effects and thus, greater treatment success.