The pharmacological properties of the alpha-adrenoceptors which increase cyclic AMP accumulation were studied in slices of rat cerebral cortex after inactivation of beta-adrenoceptors with bromoacetylalprenololmenthane. Norepinephrine increased basal cyclic AMP accumulation 2-fold, and potentiated the effect of adenosine 5-fold. The Ki and EC50 values for antagonists and agonists for both the basal and potentiated responses were generally similar to those for alpha 1-adrenoceptor-stimulated inositol phosphate accumulation in the same preparation. However, significant differences in the potencies of all agonists, and the antagonists phentolamine and BE2254 were observed between the basal and potentiated cyclic AMP responses. The differences in agonist potencies did not appear to be due to the existence of a receptor reserve. Norepinephrine, epinephrine, alpha-methylnorepinephrine and 6-fluoronorepinephrine were full agonists, while methoxamine and phenylephrine were partial agonists in both systems. The results suggest that norepinephrine increases cyclic AMP accumulation in rat cerebral cortex through alpha 1-adrenoceptors similar to those increasing phosphatidylinositol metabolism in the same tissue.