The effects of the novel ETA receptor antagonist, FR 139317, on ET-1 induced blood pressure changes were studied in the pithed Sprague-Dawley rat. FR139317 in a dose of 0.025 mg/kg b.w. had no effect while 0.05-1 mg/kg b.w. dose dependently inhibited the pressor response to an i.v. bolus injection of ET6-1 (800 pmoles/kg). While FR139317 potently inhibited the magnitide and duration of the ET-1 induced pressor response, the ETA antagonist did not significantly influence the shortlasting initial depressor response. We conclude that FR139317 in the pithed rat potently inhibits ET-1 mediated pressor responses and that this agent may become a significant tool to elucidate the putative physiological and pathophysiological role of ETA receptor mediated responses.