The purpose of the present study was to investigate the role of nitric oxide (NO) in modulating the resting vascular tone of the choroidal and anterior uveal circulations and the autoregulatory gain of the retina. Blood flow (ml/min/100 gm dry weight) to tissues was determined in 23 anesthetized piglets (3-4 kg) using radiolabelled microspheres. Ocular Perfusion Pressure (OPP) was defined as mean arterial pressure minus intraocular pressure (IOP) which was manipulated hydrostatically by cannulation of the anterior eye chamber. The OPP was decreased during intravenous infusion (30 mg/kg/hr) of either the NO-synthase inhibitor L-NAME or the inactive enantiomer D-NAME. Blood flows were determined at OPP of 60, 50, 40, 30, and 20 mmHg following initial ocular blood flow measurements. Mean initial choroidal and anterior uveal blood flows with L-NAME showed a 47+/-12% and a 43+/-6% reduction (p <.001), respectively. Mean choroidal blood flows were significantly reduced (p<.01) in the L-NAME treated animals at an OPP of 60 and 50 when compared to D-NAME. Uveal blood flows were linearly correlated with OPP in the L-NAME and D-NAME treated groups. Uveal blood flow was greater following exogenous administration of L-arginine (180 mg/kg). Mean initial retinal blood flow did not differ significantly in either group. Retinal blood flow with L-NAME was reduced at OPP of 60 mmHg and below compared to D-NAME (p<.05). The degree of compensation in the autoregulatory gain of the retinal vasculature was reduced in the presence of L-NAME at an OPP of 50 mmHg and below compared to D-NAME. These data support the hypothesis that NO may be a primary mediator in maintaining resting vascular tone to the choroid and anterior uvea in vivo and that NO blockade reduces the degree of compensation in the autoregulatory gain of the retinal vasculature within a specific range of ocular perfusion pressures.