Endothelin (ET), an endothelium-derived vasoconstrictor peptide, was injected into the jugular vein (i.v.) of guinea pigs anesthetized with urethane. Blood pressure was measured from a cannula inserted into the carotid artery. All experiments were carried out after treatment with adrenergic and cholinergic antagonists. ET showed a potent, dose-dependent pressor action in guinea pigs. However, the initial, transient depressor response which is observed in rats was not produced in guinea pigs. Nicardipine (0.1 mg/kg), a dihydropyridine Ca2+-channel blocker, significantly inhibited the ET-induced pressor response. These results suggest that ET causes a potent pressor response, which appears to be related to the activation of Ca2+ channels.