Impaired ocular blood flow is suspected to be one of the causes of normal tension glaucoma (NTG). We investigated whether endothelin (ET), a potent and continuous vasoacting peptide which was discovered recently, is associated with NTG. Plasma ET-1 levels of 52 patients with NTG but without systemic vascular or circulatory disorders were measured by radioimmunoassay, and were found to be significantly higher than those of 10 normal controls. The patients with NTG in the initial stage of visual field loss (Kosaki's classification) showed higher plasma ET-1 levels than those in the middle stage. These facts suggest that elevated plasma levels of ET-1 are correlated with NTG and its stages. We then studied the effects of ET-1 on rabbit eyes. Intravenous administration of ET-1 (10(-10) mol/kg) induced reductions in both intraocular pressure (IOP) and blood flow in the optic nerve head during three hours' observation, although it affected systemic blood pressure slightly and transiently. Blood flow in the choroid also decreased, but recovered at 90 minutes. Intravitreal injection of ET-1 (10(-5) M, 0.1 ml) also caused reductions in IOP (for 14 days) and in blood flow in the optic nerve head (during three hours' observation). Prolongation of VEP-N1 latency was observed for 14 days. These results indicate that ET-1 may be associated with NTG, especially with blood flow in the optic nerve head.