The effect of opiate ligand administration on plasma levels of atrial natriuretic peptide (ANP) was studied in awake, freely moving Sprague-Dawley rats. Prior to and following the intracerebroventricular (icv) or central venous (iv) injection of morphine (MS), leu-enkephalin (Leu-enk), dynorphin (Dyn) or beta-endorphin (B-endor), plasma samples were obtained for measurement of ANP concentrations by radioimmunoassay. MS was 10 times more potent when given icv than when given iv to increase plasma ANP levels. Icv injection of Leu-enk decreased plasma ANP concentrations. Dyn and B-endor administration (iv or icv) did not alter the plasma concentration of ANP. These effects of MS and Leu-enk on plasma concentrations of ANP appear to be mediated through actions on the central nervous system. MS, Leu-enk, B-endor, and Dyn given icv, produced elevations of plasma norepinephrine (NE) and epinephrine (Epi) concentrations. When MS was given icv, mean Epi and NE plasma levels increased 10-50 times the increases noted with B-endor, Leu-enk and Dyn. A role of catecholamines in mediating MS-stimulated ANP release is supported by the observation that ganglionic blockade with chlorisondamine significantly attenuated the increase of plasma ANP levels. MS, but not B-endor, Leu-enk and Dyn, acts within the brain to increase plasma levels of ANP. MS-induced elevations of plasma ANP levels may be dependent on an intact autonomic nervous system.