To investigate the role of endogenous prostaglandins in renin release stimulated via adrenergic pathways, isoproterenol, norepinephrine (NE) and NE in the presence of phentolamine (PTA) were infused into conscious sodium-replete rats and dogs. Isoproterenol (1 microgram.kg-1.min-1) infusion into intact rats increased plasma renin activity (PRA) eightfold. AFter pretreatment with the prostaglandin (PG) cyclooxygenase inhibitor indomethacin (5 mg/kg), isoproterenol increased PRA 16-fold. In dogs, isoproterenol (0.4 microgram.kg-1.min-1) increased PRA six-fold before indomethacin and 11-fold during PG inhibition. Infusion of NE into both rats (250 ng.kg-1.min-1) and dogs (1 microgram.kg-1.min-1) failed to increase PRA before indomethacin, but during inhibition of PG synthesis NE increased PRA in both species. During partial alpha-adrenergic blockade with PTA in dogs, PTA alone increased PRA by 38% and NE given during PTA infusion increased PRA further both before indomethacin by twofold and during PG inhibition by fivefold. In rats given NE during PTA infusion, PRA increased only after indomethacin injection. Additionally, in dogs the renin responses to these adrenergic agents were even greater after indomethacin administration than before the drug. These results in both conscious rats and dogs give no indication that renal prostaglandins mediate the renin response to adrenergic stimulation.