Early thrombolytic therapy may be beneficial for patients with acute focal cerebral ischemia. To compare the therapeutic efficacy of urokinase and heparin in acute cerebral infarction, we made a protocol for a randomized trial of intravenous (IV) urokinase and heparin begun within 12 hours of the stroke onset. Intraarterial (IA) urokinase theatment was also evaluated for the stroke within 6 hours of onset. Eligible patients had pretreatment computed tomographic scanning and gave informed consent. Forty-six patients were sutdied : 19 for IV urokinase, 19 for heparin, and 8 for IA urokinase. Baseline demographic values and risk factor profiles were similar among the respective groups. The degree of improvement on the stroke scale score after treatment in IA uroki-nase-treated group was statistically significant (p<0.05, Wilcoxon Signed Rank Test), while insignificant in IV urokinase and heparin-treated groups. Five of eight patients treated with IA urokinase improved by 4 or more points on the score or made an exellent recovery at the time of discharge, whereas similar improvement occurred in 4 patients in both IV urokinase group and the heparin group (p=0.052, Fisher's Exact Test). All of the improved patients by IA urokinase demonstrated immediate recannalization of the occluded arteries. Out of 46 study patients, there were three fatal intracerebral hemorrhages, all in IV urokinase group. These observations suggest that IA urokinase infusion within 6 hours may be safe and effica- cious for the treatment of acuted cerebral infarction. Further stydy is warranted so that the efficacy and safety of IV urokinase treatment within 6 hours can be assesed with regard to IA urokinase treatment.