In pieces of the rabbit retina, histamine (HI) had no significant effect on cAMP accumulation; however, HI inhibited forskolin-evoked accumulation of the nucleotide. Mepyramine (H1-antagonist) was without effect, while cimetidine (H2-antagonist) antagonized the HI action. Dimaprit (H2-agonist) mimicked the HI action, however its action was not significantly affected by H2-antagonists. Since phosphodiesterase (PDE) inhibitors prevented the HI action it is suggested that HI-induced inhibition of the forskolin effect results from HI-induced activation of cAMP breakdown. The muscarinic agonist carbachol, and to a lesser extent HI, both increased [3H]inositol incorporation and intensified accumulation of [3H]inositol phosphates in the rabbit retina.