In an anesthetized rat, endothelin-1 (ET-1) causes a rapid, transient fall in blood pressure followed by a large, sustained rise. Rat endothelin-3 (ET-3) differs from porcine endothelin-1 (ET-1) by six amino acids and is 20 times less potent at contracting rat aortic strips. The comparative effects of ET-3 and ET-1 on blood pressure were studied in anesthetized rats in which the arterial blood pressure was continually monitored. Dose-response curves for the contraction of rat stomach strips, guinea pig ileum, and guinea pig trachea were also constructed. In the anesthetized rat, ET-3 was slightly (but not significantly) less potent than ET-1 at producing the transient blood pressure fall but was three times less potent at causing the subsequent rise. The two peptides were equipotent at contracting rat stomach strips but ET-3 was 10 times less potent at contracting the guinea pig ileum. Rat ET-3 was less potent at contracting the guinea pig trachea and had a lower maximal effect. These results suggest the existence of multiple receptor subtypes for ET.