The presence of adenosine and its receptors in the pineal gland suggests that they could have a regulatory influence on pineal physiology. Rat pineal glands cultured in the presence of the adenosine analog 5'-N-ethylcarboxamido adenosine (NECA) promoted a significant increase in pineal adenosine 3'5'-monophosphate (cAMP) content, similar to that caused by the beta-adrenergic receptor agonist isoproterenol (ISO). A potentiation of the cAMP response occurred when the glands were simultaneously stimulated with both NECA and ISO. Whereas high cAMP levels induced by ISO were associated with an increased N-acetyltransferase (NAT) activity and rise in the melatonin production and release, the NECA-induced rise in cAMP concentration failed to promote an increase in the activity of either NAT or another pineal enzyme thyroxine 5'-deiodinase type II; likewise, pineal melatonin levels did not rise.