In this multiinstitute cooperative study, 143 patients were treated with either urokinase (UK) or combination of urokinase and dextran sulfate (UK-DS) within one to seven days following acute onset of cerebral thrombotic infarction. Of these, 81 randomized cases received a single dose of UK (2.83 X 10(5) units) by six-hour intravenous drip infusion and the remaining 62 received a combined dose of UK (2.84 X 10(5) units) and DS (3000 mg) for only one day. Moderate to marked clinical improvements assessed during the seven-day study period were observed in 30.9% of the patients treated with UK and in 61.3% of those with UK-DS, the latter being significantly higher. Hemorrhagic phenomena appeared in 3.2% of the cases treated with UK-DS and in none of those with UK alone, but mortality was 1.6% in the former and 2.5% in the latter. UK-DS produced a prompt and sustained increase in plasma fibrinolytic activity with transient and relatively minor disturbance of the blood coagulation system. The results indicate that combined therapy with UK and DS is more effective than UK alone for acute cerebral thrombotic infarction.