BACKGROUND: Drug addiction researchers have begun to study dopamine partial agonists as potential therapeutic agents. The partial dopamine D(2) receptor agonist aripiprazole has recently been tested as a treatment for stimulant and alcohol dependence in both animal and clinical studies. METHODS: A randomized and placebo-controlled pilot clinical study was conducted in a population of Chinese light and heavy smokers to assess the effect of aripiprazole on various responses to smoking. The primary outcomes were subject's ratings on questionnaires of smoking urge, withdrawal syndromes, and cigarette evaluation. Placebo, 5, and 10mg aripiprazole were acutely administered in all participants, with administrations at least 7 days apart. Subjective responses to a smoked cigarette, working memory, and attention/psychomotor performance were assessed before and after drug administration in each experimental session. Abstinence-induced smoking urge, withdrawal symptoms, blood pressure, and heart rate were also measured every 45 min after drug administration. Finally, a cue-testing session was carried out 4h after each drug administration. RESULTS: Administration of 10mg aripiprazole significantly decreased both the subjective response and psychological reward derived from smoking a cigarette in heavy smokers. While neither 5 nor 10mg aripiprazole significantly decreased abstinence-induced smoking urges or withdrawal symptoms in light and heavy smokers, these doses substantially attenuated drug cue-induced smoking urges in heavy smokers. Aripiprazole did not affect working memory or attention/psychomotor performance. CONCLUSIONS: Light and heavy smokers responded differently to aripiprazole across various dependent measures. Aripiprazole may potentially affect various subjective responses to smoking in heavy smokers.