Reocclusion of coronary arteries is a major problem after successful thrombolysis in patients with acute myocardial infarction. We evaluated in a canine model of coronary thrombosis which is known to elicit reocclusion, whether an increased single i.v. bolus dose or two boli of the novel t-PA variant BM 06.022 improved coronary blood flow after reperfusion compared to i.v. injection of a standard single dose of BM 06.022. Double bolus administration, but not an increased single bolus dose of BM 06.022 significantly increased the maximum achieved coronary blood flow, prolonged the cumulative patency time, maintained blood flow at the end of the experiments, and reduced residual thrombus wet weight. Thus, double bolus administration improves coronary blood flow after reperfusion in the dog.