The physiological role of numerically predominant alpha 2-adrenoceptor in the kidney is still unknown. This study examined the effect of alpha 2-adrenoceptor stimulation on the production of cAMP from isolated human glomeruli. Unaffected portions of human kidneys which had been removed because of renal cell carcinoma were used for the study. Glomeruli were dissected manually under a stereo microscope. In these glomeruli, alpha 2-adrenoceptor stimulation with epinephrine in the presence of propranolol inhibited significantly parathyroid hormone-dependent increases in cAMP production. This inhibitory effect of epinephrine was removed by adding a specific alpha 2-adrenoceptor antagonist, yohimbine, indicating that the inhibitory effect of epinephrine on cAMP formation was due to alpha 2-adrenoceptor stimulation. Thus, alpha 2-adrenoceptors are involved in the inhibition of cAMP production in human glomeruli.