To assess the role for intraoperative thrombolysis during surgical evacuation of massive subretinal hemorrhage, the authors studied the ability of tissue plasminogen activator (tPA) to facilitate removal of an experimental subretinal blood clot through a small drainage retinotomy. In rabbit eyes, a single subretinal injection of tissue plasminogen activator in concentrations of up to 250 micrograms/ml failed to produce significant (greater than 50%) clot dissolution during a 3-hour period. However, repetitive subretinal lavage and aspiration with tPA (50 micrograms/ml) resulted in progressive intraoperative clot dissolution in rabbits and allowed complete evacuation of blood through a small drainage retinotomy in 6 (100%) of 6 cat eyes. Repetitive vigorous subretinal irrigation with saline solution had no discernible effect on clot size in rabbit eyes. Histopathologic examination of cat eyes following tPA-assisted surgical evacuation of subretinal blood showed preservation of the outer retina in 2 eyes and severe atrophy of the outer retina in 4 eyes.