The effects of /¿-adrenergic agonists isoprenaline, fenoterol and clenbuterol on the activity of adenylyl cyclase from ciliary processes and on intraocular pressure were examined in pigmented rabbits. Isoprenaline, fenoterol and clenbuterol stimulated adenylyl cyclase activity in vitro, but clenbuterol behaved as a partial agonist. Preincubation of ciliary processes with any of these three drugs led to the heterologous desensitization of adenylyl cyclase to the stimulatory effects of beta-adrenergic agonists or vasoactive intestinal peptide (VIP). This desensitization was dose-dependent and was expressed mainly as a decrease of the highest effects of stimulatory drugs. The exact mechanism of this phenomenon is not yet known. After topical administration, all three tested /¿-adrenergic agonists decreased intraocular pressure with approximately the same intensity. The relationship between ocular hypotensive effects of /¿-adrenergic agonists and their effects on adenylyl cyclase of ciliary processes is discussed. It is concluded that ocular hypotensive effects of adrenergic agonists and other drugs stimulating adenylyl cyclase cannot be explained simply by stimulation or desensitization of adenylyl cyclase of ciliary processes.