Recent reports suggest that prostaglandins play an important role in the beta-adrenergic receptor mechanism of renin release. However, the site of the action of prostaglandins has not yet been clarified. Superfusion of rabbit renal cortical slices was used to evaluate the beta-adrenergic receptor mechanism of renin release. Renin release was stimulated by isoproterenol, prostaglandin E2, and dibutyryl cyclic AMP. Renin release stimulated by isoproterenol was inhibited by propranolol, whereas renin release stimulated by prostaglandin E2 was not inhibited by propranolol. Isoproterenol stimulated prostaglandin E2 release as well as renin release, and indomethacin inhibited these effects of isoproterenol. Propranolol inhibited prostaglandin E2 release stimulated by isoproterenol. On the other hand, indomethacin did not affect renin release stimulated by prostaglandin E2 release. Dibutyryl cyclic AMP did not stimulate prostaglandin E2 release. Indomethacin did not affect renin release stimulated by dibutyryl cyclic AMP, however, it suppressed prostaglandin E2 release during the superfusion with dibutyryl cyclic AMP. Finally, isoproterenol and prostaglandin E2 stimulated cyclic AMP release. These data suggest that prostaglandins play an important role in the beta-adrenergic receptor mechanism of renin release and the site of the action of prostaglandins is between the beta-adrenergic receptor and cyclic AMP.