The effects of neuropeptide Y (NPY) were studied on an in vitro preparation of rabbit iris dilator muscle. NPY by itself (10(-11) M to 10(-6) M) had no effect on the resting tension or on the maximal electrically-induced response (MER) of the dilator. Phenylephrine (10(-9) M to 10(-4) M) caused a dose-dependent contraction of the dilator muscle (7.8% to 40.6% of the MER). The addition of NPY 10(-6) M enhanced the phenylephrine-induced muscle contraction (8.8% to 76.8% of the MER) without altering the EC50 value (5 X 10(-6) M) of the phenylephrine dose-response curve. These findings support a modulatory role for NPY on the iris dilator muscle.