Intraocular recombinant DNA human tissue-type plasminogen activator (tPA) can promote rapid resolution of intracular fibrin clots and hyphema. The efficacy of intravitreal tPA in promoting the short-term clearance of vitreous hemorrhage was investigated. Five treatment groups with experimentally induced vitreous hemorrhage were studied. The extent of the vitreous hemorrhage was graded based on the visibility of retinal details in each quadrant. Two weeks following intravitreal tPA injection (50,000 IU), the nonvitrectomized group and gas vitrectomy groups, each of which received a single tPA injection, showed a statistically significant reduction of the vitreous hemorrhage, although this was thought to represent only a modest clinical effect. Tractional retinal detachments were noted to develop more frequently in tPA-treated eyes as compared with controls.