The effect of topical unilateral application of lofexidine, an α2-agonist, on ocular regional blood flow was tested in anesthetized rabbits using radiolabeled microspheres. A significant reduction in blood flow was found only in the ciliary body of the treated eye at 1 hr after lofexidine treatment. However, the IOP of both eyes was decreased significantly at 30 and 60 min post lofexidine treatment. Yohimbine (i.v.) blocked this IOP lowering effect, but only partially prevented the blood flow response. In addition, no significant difference was found in either basal or amphotericin-B stimulated short-circuit current or potential difference of the isolated rabbit iris-ciliary body after 30 minutes of lofexidine treatment. These observations suggest that the IOP lowering effect of lofexidine appears to be mediated by α2-receptors but unrelated to the reduction in the ocular blood flow and net electrogenic ion transport.