OBJECTIVES: Capsaicin, the pungent analgesic substance of the red pepper, is known to affect central opioid activities, which is one of the most important factors to alcohol intake behavior. The purpose of this study was to investigate whether systemic administration of capsaicin affects alcohol intake in C57BL/6 mice. METHODS: After intraperitoneal administration of 0.01 mg/kg of capsaicin with a vehicle or the vehicle alone as the control for eight days in C57BL/6 mice on a limited access alcohol model, capsaicin's effects on 2-hour alcohol, 22-hour water, 24-hour food intake and body weight were studied. RESULTS: 1) For 2-hour alcohol intake, a repeated measures ANOVA (2 drug treatment groups repeated across 5 two-day blocks) yielded a significant group by block interaction (p<0.05). The independent t-test showed that significant suppression of 2-hour alcohol intake was observed when subjects were administered with capsaicin compared with the vehicle alone across the last three 2-day blocks (p0.05). The paired t-test revealed that significant suppression of 2-hour alcohol intake was observed when subjects were administered with capsaicin compared with before capsaicin administration across the last two 2-day blocks (p0.01). But there is no significant difference of 2-hour alcohol intake when subjects were administered with the vehicle alone compared with before vehicle administration. 2) A repeated measures ANOVA revealed no significant group by block interaction for 22-hour water intake, 24-hour food intake, or body weight. CONCLUSION: These results show that capsaicin administration can affect alcohol intake behavior and also suggest that food culture might affect drinking behaviors.