The influence of trifluoperazine (TFP) treatment on angiotensin II-induced inhibition of renin release from the rat isolated perfused kidney was examined. Angiotensin II, 1 mumol/l, in the presence of 1 mmol/l calcium, reduced basal renin secretion by 70%. When calcium was omitted from the perfusion medium, inhibition of renin release no longer occurred. Pretreatment of the rat isolated perfused kidney with the calmodulin inhibitor trifluoperazine (TFP), 10 mumol/l for 6 min, interfered with the inhibitory action of angiotensin II on renin release as well as angiotensin II-induced renal vasoconstriction. Our data suggest a role for calmodulin in mediating the effects of angiotensin II on both renin release and renal vascular resistance.