THE AUTHORS REPORT the results of a retrospective review, between January 1986 and December 1991, of the results of early surgery and intrathecal thrombolytic therapy in 111 patients with aneurysmal subarachnoid hemorrhage. Effects on clot lysis, angiographic and symptomatic vasospasm, cerebral infarction, and clinical outcome were compared in 60 patients treated with urokinase (UK) 60,000 IU/d for 7 days (UK group), 22 patients treated with 0.042 to 1 mg tissue plasminogen activator (tPA) every 6 to 8 hours for 5 days (tPA group), and 29 patients who did not receive treatment with either thrombolytic agent (no-treatment group). The no-treatment group consisted of all patients treated before July 1986 and of patients in whom thrombolytic therapy was attempted but failed to start or in whom the therapy was not used intentionally because of small subarachnoid clot. Treatment with UK was employed between July 1986 and March 1991, and tPA was employed during the remainder of the study for patients at a higher risk for vasospasm. The severity of angiographic vasospasm and the incidence of infarction in the UK and the tPA groups were less than those of the no-treatment group (P < 0.01), in spite of a larger amount of initial subarachnoid blood clot in both thrombolytic groups. This appears to be the result of the more rapid clearance of cisternal clot in the thrombolytic groups than the no-treatment group (P < 0.01). Only tPA therapy reduced the incidence of symptomatic vasospasm (P < 0.05). No serious complications were observed, although in the tPA group, asymptomatic intraventricular hemorrhage occurred in one patient, and transient confusion in another. Both received 4 mg tPA/d. Meningitis was suspected in 16 patients of the UK group. However, in this relatively small retrospective series, there were no differences among the three groups in overall outcome at 3 months. This study indicates that postoperative intrathecal thrombolytic therapies, especially with less than 4 mg/d of tPA, are effective in lysing subarachnoid clot and preventing vasospasm and infarction safely.