The traditional definition of glaucoma as a disorder of increased intraocular pressure (IOP) oversimplifies the clinical situation. Some glaucoma patients never have higher than normal IOP and others continue to develop optic nerve damage despite maximal lowering of IOP. Another possible factor in the etiology of glaucoma may be regulation of the regional microvasculature of the anterior optic nerve. One reason to believe that microvascular factors are important is that many microvascular diseases are associated with glaucomatous optic neuropathy. In this study, endothelin-1 was used to produce vasoconstriction of the ocular vasculature following both intravitreal and perineural delivery. Intravitreal injections (1.25 and 2.50 micrograms) were given to six rabbits to assess the vascular response of the posterior segment. In addition, endothelin (0.0-4.2 micrograms) was delivered with an osmotically driven minipump system to the perineural region of six rabbits. Vasoconstriction of the anterior optic nerve vasculature was observed following both methods of endothelin delivery. A better understanding of the microvasculature of the anterior optic nerve is needed to evaluate its relationship to glaucomatous damage. Modulation of this vascular supply, with agents that mimic autoregulatory controls, may allow the sites of vasomotor control to be established and, in the future, their status to be manipulated.