The inhibitory effect of neuropeptide Y (NPY) was studied on the adenylate cyclase (AC) activity in homogenates of rabbit ciliary processes and compared with that of theα2-adrenergic agonist clonidine (CLN).NPY inhibited basal AC activity as well as AC activity stimulated by isoprotere-nol (ISO), vasoactive intestinal polypep-tide (VIP) or forskolin (FSK). The extent of this inhibition corresponded well to the inhibition elicited by CLN. The inhibitory effects of NPY and CLN appeared to be nonadditive. AC activity stimulated by ISO was considerably more sensitive to the effects of either NPY or CLN than basal, VIP- or FSK-stimulated AC activity.It was inferred that NPY inhibitory effects were mediated by the activation of NPY receptors coupled negatively to the catalytic unit of AC via the inhibitory G1protein. Moreover, involvement of NPY in physiological modulation of AC activity in ciliary processes and in the regulation of aqueous humor formation and intraocular pressure is suggested.