To explore the feasibility of using human recombinant tissue-type plasminogen activator in the management of subretinal hemorrhage, we examined the toxic effects of a commercial preparation of human recombinant tissue-type plasminogen activator in the subretinal space of the holangiotic retina of the cat. Various concentrations of human recombinant tissue-type plasminogen activator and controls were infused into the subretinal space with a glass micropipette (40- to 60-microns tip) to form a retinal bleb. Concentrations from 2.5 mg/L to 200 mg/L were well tolerated without ultrastructural toxic effects, while 1000 mg/L of human recombinant tissue-type plasminogen activator caused severe, irreversible toxic effects to the photoreceptor-retinal pigment epithelium complex. This toxic effect appeared to be due to the carrier vehicle rather than the human recombinant tissue-type plasminogen activator protein itself. Our results demonstrate that commercially prepared human recombinant tissue-type plasminogen activator can be safely used in the subretinal space of the cat with the range necessary for fibrinolysis.