Seventeen patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were treated with heparin combined with intravenous singlechain urokinase-type plasminogen activator (scu-PA), obtained by expression of the cDNA encoding mature human scu-PA in Escherichia coli. In eight patients, recombinant scu-PA (rscu-PA) was given as a 10 mg bolus followed by 30 mg over 1 hr. Recanalization was obtained in six patients, but with persistent delayed opacification of the vessel in four of these patients. During infusion, a plateau level of rscu-PA antigen in plasma of 3.4 gtg/ml (median value, range 1.4 to 5.5) was reached. At the end of the infusion the a2-antiplasmin level had decreased to 54% (median, range 22% to 82%) of the preinfusion level, the fibrinogen level to 89% (median, range 26% to 101%), and fibrinogen degradation products (FDPs) to 20, g/ml (median, range 8 to 387). In nine patients, rscu-PA was administered as a 10 mg bolus followed by 60 mg over 1 hr. This resulted in recanalization with normal distal filling of the vessel in seven patients, within 46 17 min (mean + SD). During infusion the concentration of rscu-PA in plasma increased to a median value of 7.4, ug/ml (range 4.0 to 13.3). At the end of the infusion the a2-antiplasmin level was 22% of baseline (range 5% to 47%), the fibrinogen level 45% (range 4% to 94%), and the concentration of FDPs 87 gg/ml (range 6 to 1034). No significant bleeding or short-term side effects were observed. After the end of the infusion the disappearance of rscu-PA antigen from plasma in both groups could be described as a sum of two exponential terms. Ninety-five percent of the plasma disappearance occurred with a tl/2 of 7.9 min and 5% with a: tl/2 of 48 min. Thus intravenous rscu-PA at a sufficiently high infusion rate can produce fibrin-specific coronary thrombolysis in patients with acute myocardial infarction. However, its infusion is associated with a variable degree of systemic fibrinolytic activation, which particularly at higher infusion rates. may result in extensive fibrinogen breakdown,