Several evidences have indicated that many nuclei in the brain have critical role in water intake. Angiotensin II is one of the most important neurotransmitters involved in regulation of fluid homeostasis. In this study, the interaction of i.c.v. injection of captopril and histamine on water intake in adult male water-deprived rats was investigated. Rats were implanted with guide cannula aimed toward lateral ventericle. After recovery period, the animals deprived of water for 24 h, and then, drugs were injected and the volume of water intake was measured for 1 hour. The results showed that captopril (7 and 10 µg/rat) decreased, while histamine (40 and 80 µg/rat) increased the rate of water intake. Meanwhile, captopril pretreatment blocked the responses induced by histamine. These data suggest that histamine and angiotensin systems may have an interaction on water intake mechanism.