Dose-dependent tension curves were recorded from the in vitro toad aortas by administration of endothelin-1 and sarafotoxin-S6b. The maximal contractile tensions by both drugs were evoked at a 10(-8) M concentration. By a single dose application (10(-8) M) of endothelin-1 and sarafotoxin-S6b to both endothelium-preserved and denuded vessels, the induction of the endothelium-dependent vasocontraction occurs after 2 min of administration. Ultrastructural changes of Weibel-Palade bodies such as decrease in electron density, swelling with a wide peripheral halo, and expulsion of their contents in a manner of exocytosis become evident within 2 min after administration of these drugs. These findings indicate that some vasocontractile substances in Weibel-Palade bodies are extracellularly discharged by endothelin-1 and sarafotoxin-S6b.