Simple aspiration to remove acute intracerebral hematomas has been thwarted by the solidity of the clot. Urokinase, a first generation fibrinolytic agent, has been used to liquefy such clots with some success. Therefore, tissue plasminogen activator (t-PA), a second generation fibrinolytic drug that may be safer and more effective, was studied to evaluate its ability to lyse clot in vitro and its reactivity in the brain and subarachnoid space. t-PA seems to cause partial clot lysis in small dosages (3750 units/70-cc clot) and in a short time (15 minutes). It seems to perfuse through the clot when injected in one place. It does not cause inflammation or bleeding when injected into the rat brain, but indeed seems to promote resorption of blood when the two are injected together. It does not cause aseptic meningitis when injected into the cisterna magna of rabbits. t-PA may prove to be an important adjuvant to the stereotactic aspiration of intracerebral hematomas. It may be particularly helpful in lysing these clots to make possible more gentle aspiration, removing the risk to surrounding brain of strong vacuum.