The effects of ecopipam (a D(1) selective antagonist) or triazolam pretreatment on the subjective and physiological effects of intravenously administered nicotine were examined in 10 cigarette-smoking cocaine abusers. Under double-blind, randomized conditions, subjects received oral capsule pretreatment (0, 30 or 100 mg ecopipam, or 0.25 mg/70 kg triazolam), followed 120 min later by an intravenous injection of 2 mg/70 kg nicotine or saline. Subjective ratings, heart rate and blood pressure were assessed before and repeatedly after each intravenous injection. Compared to oral placebo pretreatment, both ecopipam and triazolam pretreatment produced significant elevations in subject-reported capsule effect and observer ratings of sleepiness/sedation. Nicotine increased ratings of 'drug effect', 'rush', 'high', 'stimulated', 'liking', 'good effects' and 'bad effects', and produced modest increases in heart rate and blood pressure. Following both intra-venous saline and nicotine injection, ecopipam tended to reduce heart rate and blood pressure. Although both ecopipam and triazolam lowered several subjective ratings following intravenous saline injection, neither ecopipam nor triazolam affected nicotine subjective effects. In contrast to Romach et al. (Arch Gen Psychiatry 56: 1101-1106, 1999), who showed that pretreatment with ecopipam blocked cocaine subjective effects, the current study found no attenuation of the subjective effects of nicotine, and thus, provides no support for the hypothesis that D(1) receptors mediate the cocaine-like subjective effects of nicotine.