Intravitreal fibrin clots were produced by intravitreal injection of 0.2 ml of autologous plasma in 62 rabbit eyes. The intravitreal injection of 0.25 micrograms or more of tissue plasminogen activator(tPA) resulted in a total clearing of intravitreal fibrin within one day in all treated eyes. This was significantly faster than in the control eyes, in which complete clearing was not seen until 8 days later. This represents the plateau on the dose-response curve in doses ranging from 0.25 to 200 micrograms. With light microscopy and transmission electron microscopy, retinal toxicity was demonstrated in eyes enucleated seven days after injection of 25 micrograms or more of tPA. This study demonstrates that tPA was effective and safe at 12.5 micrograms or less in clearing intravitreal fibrin in an experimental model. These results suggest that low dosages of tPA, probably of 3 micrograms or less, may be useful in the treatment of severe postvitrectomy fibrin formation seen clinically.