Arginine-vasopressin (AVP), angiotensin II (AII), and norepinephrine (NE) are known to stimulate prostaglandin (PG) synthesis in the intact rat kidney perfused with Tyrode's solution by a mechanism that requires intracellular Ca2+, while PG synthesis elicited by bradykinin (BK) is independent of Ca2+. To elucidate further the differences in the mechanism of action of BK and other vasoactive agents, in this preparation we have investigated the effect of 1) caffeine, an agent known to interfere with the uptake and storage of Ca2+in intracellular sites, on renal output of PGE2and 6-keto-PGF1αelicited by AVP, AI, NE, and BK; 2) various combinations of the maximal doses of BK, All, AVP, and NE on renal PG synthesis; and 3) RHC 80267, an inhibitor of diglyceride and monoglyceride lipase, on the output of PGs produced by these vasoactive agents. Infusion of 1 mM caffeine inhibited PG output elicited by AVP, AII, and NE but not that caused by BK in the absence of extracellular Ca2+. Combined administration of maximal doses of BK (2.8 nmol) with that of AII (0.28 nmol), AVP (0.27 nmol), or NE (3.2 nmol) but not AVP and AII, NE and AVP, or NE and AII produced an additive effect on renal PG output in the presence or absence of Ca2+. The renal vasoconstrictor effect of AVP, AII, and NE produced in the presence of Ca2+was not additive and remained unaltered when given together with BK. Administration of 12 μM RHC 80267 attenuated BK-induced renal PG output in concentrations that did not alter the effect of either AVP, AII, or NE to increase PG output or renal vasoconstriction in the presence of Ca2+. These data suggest that BK stimulates renal PG synthesis by a mechanism that is different from that of other vasoactive agents and probably involves activation of a distinct lipase that releases arachidonic acid from diglycerides or monoglycerides derived from phospholipids or triglycerides.