Abstract Antioxidant effects upon renal production of both prostaglandins and cAMP were investigated using slices of rat inner medulla. Synthetic antioxidants were more potent inhibitors of prostaglandin production than were naturally occurring antioxidants. Synthetic compounds 2,7-naphthalenediol, and Santoquin ® (Ethoxyquin) caused a 60% inhibition of prostaglandin E 2(PGE 2) synthesis at a concentration of 0.01 m M. Ascorbic acid caused only a 30% inhibition at a concentration of 10 m M. Antioxidant inhibition of prostaglandin production was also observed following arachidonic acid addition. Antioxidants that reduced PGE 2 synthesis also reduced PGF 2α synthesis. Test agents found to reduce prostaglandin synthesis also lowered cAMP content. 2,7-Naphthalenediol elicited a dose-dependent decrease in both prostaglandin synthesis and cAMP content. While PGE 1 did not increase cAMP in control slices, the low cAMP level produced by Santoquin was increased to control values by PGE 1. Furthermore, Santoquin and 2,7-naphthalenediol did not alter arginine vasopressin-stimulated cAMP content. By contrast, inhibition of the arginine vasopressin stimulation by butylated hydroxyanisole suggested additional effects by this agent. These results are consistent with the hypothesis that endogenously produced PGE 2 can exert a hormonelike action in the inner medulla by increasing cAMP content. Advantages of the inner medullary slice system compared to homogenates for investigation of the actions of antioxidants or other agents thought to alter prostaglandin synthesis are discussed.