It is unclear whether the diuretic effects of atrial natriuretic peptide (ANP) result, in part, from an inhibition of the renal actions of vasopressin. Moreover, accruing evidence suggests that the kidneys themselves may produce an ANP-like peptide, urodilatin, which shares many of the renal actions of ANP. The mechanism underlying the diuretic action of urodilatin has not yet been examined. Accordingly, we have investigated the potential modulatory actions of both ANP and urodilatin on vasopressin-stimulated cyclic AMP (cAMP) production in microdissected inner medullary collecting duct (IMCD) segments of rat kidney. ANP and urodilatin alone (at 10(-8) or 10(-6) M) had no demonstrable effect on cAMP accumulation in IMCD segments. Moreover, neither ANP nor urodilatin (each at 10(-6) M) significantly altered either the profile or the absolute magnitude of the cAMP response stimulated by vasopressin. These findings indicate that neither ANP nor urodilatin interacts with the vasopressin-sensitive adenylate cyclase site in the rat IMCD to contribute to its diuretic actions.