To investigate the effect of endothelin on renin release, experiments were performed in barbiturate-anaesthetized dogs with denervated kidneys. Intrarenal infusion of endothelin (1 ng min-1 kg-1 body wt) reduced renal blood flow (RBF) from 145 +/- 10 ml min-1 to 98 +/- 9 ml min-1 without altering renin release (1 +/- 1 microgram angiotensin I (AI) min-1). Renin release was then increased either by renal arterial constriction or ureteral occlusion. When renal arterial pressure was reduced to 50 mmHg, renin release averaged 79 +/- 20 micrograms AI min-1 in six dogs and fell significantly to 24 +/- 6 micrograms AI min-1 during endothelin infusion. During ureteral occlusion the inhibitory effect of endothelin on renin release either during inhibition of beta-adrenergic activity with propranolol or after inhibiting prostaglandin synthesis by indomethacin during intrarenal infusion of isoproterenol was examined. After propranolol administration ureteral occlusion increased renin release from 5 +/- 2 micrograms AI min-1 to 38 +/- 12 micrograms AI min-1 in six dogs. Subsequent intrarenal endothelin infusion (1 ng min-1 kg-1 body wt) during maintained ureteral occlusion reduced renin release to 10 +/- 3 micrograms AI min-1. In six other dogs prostaglandin synthesis was inhibited by indomethacin. Subsequent infusion of isoproterenol (0.2 microgram min-1 kg-1 body wt) to stimulate beta-adrenoceptor activity increased renin release from 13 +/- 4 micrograms AI min-1 to 68 +/- 8 micrograms AI min-1 during ureteral occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)