The role of the adrenal medulla in the regulation of renal cortical adrenergic receptors was investigated in renal cortical particulate fractions from control rats and rats 6 wk after adrenal demedullation. The specific binding of [3H]prazosin, [3H]rauwolscine, and [125I]iodocyanopindolol were used to quantitate alpha 1-, alpha 2-, and beta-adrenergic receptors, respectively. Adrenal demedullation increased the concentration of all three groups of renal adrenergic receptors; maximal number of binding sites (Bmax, per milligram membrane protein) for alpha 1-, and alpha 2-, and beta-adrenergic receptors were increased by 22, 18.5, and 25%, respectively (P less than 0.05 for each). No differences were found in the equilibrium dissociation constants (KD) for any of the radioligands. Plasma corticosterone and plasma and renal norepinephrine levels were unchanged, whereas plasma epinephrine was decreased 72% by adrenal demedullation (P less than 0.01); renal cortical epinephrine was not detectable in control or demedullated animals. Our results suggest that, in the physiological state, the adrenal medulla modulates the number of renal cortical adrenergic receptors, presumably through the actions of a circulating factor such as epinephrine.