Purpose: The purpose of this study was to evaluate blood flow reduction to the optic nerve after chronic administration of endothelin-1 in primates. Materials and Methods: Endothelin-1 (three rhesus monkeys), in a dosage of 0.1 mu g/day, or balanced salt solution (three rhesus monkeys) was delivered to the perineural region of the anterior optic nerve via osmotically driven minipumps. Optic nerve blood flow was determined by means of a colored microspheres technique after 7 days of local endothelin-1 or balanced salt solution administration. The effect of endothelin-1 on optic nerve blood flow was analyzed by analysis of convariance (ANCOVA) in a 2 (between groups: endothelin-1, balanced salt solution) x 2 (within subject: blood flow minipump optic nerve, blood flow controls) design, with intraocular pressure as a changing covariate. Results: The decrease of optic nerve blood flow in the endothelin-1 eyes was significant compared to the balanced salt solution eyes (ANCOVA p = 0.015). Among the monkeys implanted with endothelin-1 minipumps, the decrease in optic nerve blood flow in the experimental eye compared to the contralateral eye (mean +/- SD 35.7 +/- 9.1%) was significant (p = 0.01), while that among the monkeys implanted with balanced salt solution minipumps (mean +/- SD 0.7 +/- 5.5%) was not (p = 0.73). Conclusions: This new primate model of chronic optic nerve ischemia may represent a method to evaluate experimentally the implication of a local hemodynamic perturbation in various optic neuropathies.