To assess the effect of urokinase-induced reduction of fibrinogen concentration on myocardial perfusion, urokinase infusions were administered for 3 months to 24 men (mean age 59 +/- 10 years) in the inoperable end-stage of coronary heart disease with treatment-resistant angina pectoris. Initially 500,000 IU urokinase were infused i.v. daily until a fibrinogen concentration of 150-200 mg/dl was reached. Treatment was then continued as out-patients at a dosage of 500,000 IU two to four times per week. After 12 weeks the fibrinogen concentration had fallen from 348 +/- 88 to 211 +/- 52 mg/dl and plasma viscosity from 1.44 +/- 0.08 to 1.33 +/- 0.09 mPa.s (P for each less than 0.01). Up to the end of 12 weeks after the end of treatment the frequency of anginal attacks fell significantly from 3.2 +/- 1.6 to 0.7 +/- 0.4 daily (P less than 0.01), while ergometric exercise capacity increased by 76%. Thallium myocardial scintigraphy demonstrated an increased perfusion in all but three of 19 patients, global in 10, regional in 6. These results indicate that in patients with treatment-resistant angina due to coronary heart disease chronic intermittent urokinase infusion provides a promising treatment alternative.