The receptor subtype mediating the antidipsogenic effects of the endothelins (ETs) was determined in conscious, unrestrained, normally hydrated rats. Intracerebroventricular injection of 6, 12, and 20 ng ET-2 resulted in a significant, dose-related inhibition of water drinking in response to subsequent injection of 100 pmol angiotensin II (ANG II). Pretreatment with 50 or 100 ng ET-B receptor agonist failed to alter the subsequent drinking response to ANG II. Drinking in response to ANG II was significantly accentuated in rats pretreated with 50, 100, and 200 ng of the selective ET-A receptor antagonist BQ-123. These data indicate that the antidipsogenic effects of the ETs are mediated via the ET-A receptor subtype and further suggest that endogenous ET plays a physiologically relevant role in the central nervous system control of fluid and electrolyte homeostasis.