The adrenergic control of cAMP and cGMP in dispersed adult rat pinealocytes was investigated. Norepinephrine treatment increased cAMP and cGMP content 60- and 400-fold, respectively; both .alpha.- and .beta.-adrenoceptors had to be activated for these responses to occur. .beta.-Adrenergic stimulation alone produced only .apprx. 6- and 2-fold increase in cAMP and cGMP content, respectively. .alpha.-Adrenergic stimulation, which alone had no effect on either cyclic nucleotide concentration, markedly amplified the .beta.-adrenergic stimulation of both cAMP and cGMP. The relative potency of .alpha.-adrenergic agonists and antagonists indicates the .alpha.1-subclass of adrenoceptors is involved. A role of .alpha.1-adrenoceptors in the control of pineal cAMP is consistent with published evidence of the presence of .alpha.1-adrenoceptors on pinealocytes, and their role in the regulation of N-acetyltransferase activity and melatonin production.