Nitric oxide generated by three distinct enzyme systems appears to play a critical role in many diverse physiological processes. Using both conventional and immunohistochemical techniques, nitric oxide synthases have been identified throughout the body, including all regions of the eye. A large number of in vitro and in vivo preparations have been utilized showing nitric oxide to have an important role in regulation of regional ocular blood flow. Nitric oxide-mediated control of basal ocular blood flow is demonstrated by vasoconstriction seen in experiments where vascular endothelial cells are removed, or when nitric oxide synthase is inhibited. The endogenous source of nitric oxide in the eye appears to be both endothelial and neural. In addition, administration of drugs that can 'donate' nitric oxide produces vasodilation of the eye vasculature. Local vasodilation in response to illumination of the retina is controlled by generation and release of nitric oxide, whereas most other physiological adjustments of ocular blood flow (i.e., autoregulation and responses to altered blood gas levels) seem to be relatively independent of nitric oxide mechanisms. Nitric oxide is implicated in a variety of ocular pathophysiological states including uveitis, retinal ischemic disease, diabetes and glaucoma.