Flash electroretinograms (ERG) were recorded in the rabbit eye submitted to high intraocular pressure (HIOP) induced by the suction-cup method. When intraocular pressure rose to 100 mmHg, ERG was suppressed but rapidly recovered even under HIOP when animals were pre-treated either intravitreously with a nitric oxide donor, sodium nitroprusside, or intravenously with free radical scavengers, superoxide dismutase (SOD)+catalase. In contrast, injection of a nitric oxide synthesis inhibitor, nitro-L-arginine, into the vitreous cavity inhibited the protective effect of SOD+catalase during HIOP-induced ERG extinction. These results suggest that nitric oxide could play a role in the regulation of ocular vessel tone and that severe ischemia can impede this effect through oxygen-derived free radical generation.