Renal prostaglandin E2 (PGE2) synthesis is enhanced by exogenous vasopressin (AVP). To determine whether the pressor or the antidiuretic activities of AVP are related to its effect on PGE2 synthesis, AVP and the nonpressor analog, 1-deamino-8-D-arginine vasopressin (dD'AVP), were administered to the isolated perfused rabbit kidney, PGE2 was measured in the renal venous effluent by RIA and validated by bioassay. AVP in doses of 20, 200, and 2,000 ng progressively increased perfusion pressore by 12.1 +/- 2.4, 62.0 +/- 7.9, and 74.3 +/- 13.5 mm Hg, respectively, and increased PGE2 by 28 +/- 7, 80 +/- 3, and 129 +/- 57 ng/50 ml effluent, respectively. Bradykinin and angiotensin II induced a similar dose response on PGE2 release. However, dD'AVP in doses up to 20,000 ng minimally enhanced PGE2 release (20 +/- 16 ng/50 ml) and did not alter perfusion pressure. Simultaneous administration of AVP (200 ng) with the specific AVP pressor antagonist, d-cyclo-O-methyl-tyrosine-AVP, in a 1:10 (agonist to antagonist) weight ratio blunted the increase in perfusion pressure by 59 +/- 9% and blunted the increase in PGE2 release by 59 +/- 10% (P < 0.05). In a 1:100 weight ratio, the pressure antagonist reduced the AVP pressure response by 86 +/- 6% and reduced PGE2 by 84 +/- 7% (P < 0.01). These data suggest that the AVP stimulation of renal PGE2 synthesis is related primarily to its pressor and not to its antidiuretic activity in this in vitro kidney model. (Endocrinology 108: 495, 1981)