Twenty-five micrograms of human recombinant tissue plasminogen activator (tPA) was injected intracamerally into the eyes of three aphakic patients who developed severe intraocular fibrin formation within 24 hours after vitrectomy surgery. Fluid obtained from gas-fluid exchange specimens taken 24 hours after tPA injection was analyzed for tPA by an enzyme-linked immunosorbent assay and a spectrophotometric solid-phase fibrin assay. In each of the three patients, complete fibrin resolution occurred within four hours after the tPA injection. There were no complications associated with the intraocular tPA injections. There was measurable tPA activity 24 hours after the initial injection ranging from 0.23 to 1.4 micrograms. In contrast, tPA was undetectable in gas-fluid exchange specimens obtained from seven patients who did not receive intraocular tPA injections. Intraocular tPA is an effective means of treating postvitrectomy fibrin formation in selected aphakic patients.