The local infusion of urokinase may be complicated by hemorrhage. Except for maintaining fibrinogen levels above 100 mg/dL, no other criteria exist for titrating the dose of urokinase to avoid hemorrhagic complications. A retrospective examination of the fibrinolytic and coagulation states was performed on 11 patients receiving local high-dose urokinase (240,000 U/hr) and heparin for thrombolysis of acute occlusions to identify parameters other than fibrinogen levels that may correlate with bleeding complications. Five patients experienced bleeding complications, 3 of whom had partial thromboplastin time (PTT) values greater than 150 seconds. None of the five patients having hemorrhagic complications had fibrinogen levels below 100 mg/dL at any time. Urokinase began to enhance the effect of heparin on PTT values as a result of reducing fibrinogen levels. In 10 of 11 patients this effect caused PTT values to at least double when compared with heparin alone. This substantial rise in PTT occurred only after fibrinogen levels approached 200 mg/dL in 8 of 11 patients. Although the number of patients is small, these data suggest that when heparin is used during thrombolysis, closer PTT monitoring should be carried out as fibrinogen levels begin to decline, especially when they approach 200 mg/dL, to avoid excessive PTT elevations and subsequent bleeding.