&NA;Premature lysis of subarachnoid blood clots by thrombolytic substances such as urokinase and plasmin has been shown to be efficacious in preventing cerebral vasospasm in clinical and experimental investigations. Recently, tissue plasminogen activator (rtPA) derived from recombinant deoxyribonucleic (DNA) technology has been introduced as a new thrombolytic substance. With its high affinity for fibrin‐bound plasminogen and low affinity for circulating plasminogen by which a clot‐selective fibrinolysis can be achieved without the danger of inducing systemic fibrinogenolysis, rtPA might be the ideal substance for the postoperative lysis of cisternal blood accumulations after subarachnoid hemorrhage. The efficacy of rtPA in preventing delayed cerebral vasospasm after experimental subarachnoid hemorrhage using a single intracisternal bolus injection of this agent was investigated. With a single injection of 25 &mgr;g of rtPA into the cisterna magna 48 hours after the first and 6 hours after the second injection of blood in the two‐hemorrhage model of cerebral vasospasm, angiographic spasm of the basilar artery was completely prevented in all animals so treated whereas in the control group severe vasospasm occurred. Autopsy studies of the experimental animals demonstrated that the subarachnoid blood clots were almost completely removed by intracisternal rtPA application. Additionally the pathomorphological signs of proliferative vasculopathy present in all animals of the control group were not demonstrable in the rtPA group. As intracisternal bolus injection of rtPA is highly efficacious in preventing angiographic as well as pathomorphological vasospasm, it is concluded that use of this thrombolytic substance might be a promising approach for pharmacological blood clot removal. (Neurosurgery25:590‐598, 1989)