Inhibition of ciliary process adenylate cyclase was studied on rabbit membrane preparations. When considered individually, epinephrine, GTP and NaCl did not inhibit adenylate cyclase activity. On the other hand, when present together, epinephrine, GTP (10(-5) M) and NaCl (200 mM) acted synergistically to cause a 27% inhibition of basal activity. A similar inhibition was observed with 1-norepinephrine. Clonidine and BHT 920, two alpha 2-agents were found to be partial agonists causing 63% and 82% as much inhibition as epinephrine. Phenylephrine, an alpha 1-agonist did not inhibit adenylate cyclase activity at concentrations up to 10(-4) M. Yohimbine and phentolamine prevented the inhibition of adenylate cyclase by epinephrine, while prazosin was ineffective. Alpha 2-receptor selectivity in rabbit ciliary processes and their negative coupling to an adenylate cyclase via a NaCl-dependent GTP binding protein, Ni, is thus well established.