Background: Urokinase or two-chain urokinase-type plasminogen activator has been shown to be effective in the treatment of acute myocardial infarction. Its parent molecule, single-chain urokinase-type plasminogen activator (scu-PA), unlike urokinase, can selectively activate fibrin-bound plasminogen. The induced clot lysis is amplified by plasmin-triggered conversion of scu-PA to urokinase and by further plasmin generation. The aim of our study was to compare the efficacy and safety of recombinant unglycosylated scu-PA, or saruplase, and urokinase at doses considered optimal in patients with acute myocardial infarction within 6 hours of onset of pain. Methods and results: In a double-blind trial 543 patients were randomized to saruplase (20 mg bolus + 60 mg/hr) or urokinase (1.5 million unit bolus + 1.5 million units/hr). Primary endpoint: The patency rates at 24-72 hours were 75.4% (95% CI 70.3-80.5%) for saruplase and 74.2% (95% CI 69.0-79.4%; P = 0.77) for urokinase. Secondary endpoint: The incidence of bleeding events in both groups was 10.7%. There were three hemorrhagic strokes in the saruplase group (ns). Other efficacy and safety evaluations: Apart from the generation of more fibrinogen degradation products under saruplase, the changes in hemostatic parameters did not differ. Hospital mortality was 4.4% for saruplase and 8.1% for urokinase. This nonsignificant difference was maintained for 1 year. Conclusion: The efficacy and safety of saruplase and urokinase in the regimens used are very similar.