Alpha 2-Adrenoceptors are known to inhibit adenylate cyclase in a number of tissues, but their function in the kidney is unknown. Adenylate cyclase and sodium excretion were stimulated with furosemide (30 microM) in the rat kidney perfused with Krebs-Henseleit solution (albumin 6.5 g/100 ml, 36 degrees C). beta-Adrenoceptors and alpha 1-adrenoceptors were blocked by propranolol (100 nM) and prazosin (30 nM) in the perfusate. Urinary cAMP and sodium excretion increased with furosemide. Activation of alpha 2-adrenoceptors with epinephrine (28 nM) caused no change in perfusion pressure or flow but decreased urinary cAMP and sodium excretion. These effects of epinephrine were reversed by the alpha 2-selective adrenoceptor blocking agent yohimbine (300 nM). Thus, in the setting of furosemide-stimulated sodium excretion and an associated elevation of adenylate cyclase, alpha 2-adrenoceptor stimulation resulted in sodium retention and inhibition of adenylate cyclase. By this receptor mechanism the sympathoadrenal system may contribute to retention of sodium.