Human retinal pigment epithelial cells in culture demonstrate adenylate cyclase activity. It is membrane-bound and modulated by GTP regulatory proteins. It is effectively activated only by beta-adrenergic agonists (L-isoproterenol greater than or equal to L-epinephrine greater than L-norepinephrine) and some prostaglandins (PGE1 and PGE2, but not PGF1 alpha). The adrenergic response appears to be mediated by beta-2 receptors. No inhibitory ligands could be demonstrated. Its characteristics, which are similar to functional adenylate cyclase complexes in other mammalian cells, and its selective and sensitive agonist responsiveness, suggest a possible physiologic role in the regulation of human retinal pigment epithelial-cell function.