BACKGROUND: Comparison of different plasminogen activators is difficult because conventional endpoints such as mortality are relatively insensitive to potential differences in efficacy with respect to rapidity of recanalization of infarct-related arteries. METHODS: This study was performed to determine whether valid comparisons could be made by means of biochemical endpoints that have been demonstrated previously to permit estimation of the time of opening of an infarct-related artery in experimental animals and in patients. The method is based on time-dependent interconversion of isoforms of creatine kinase mediated by carboxypeptidase N, an enzyme present in excess in circulating blood. A small subset of 39 patients studied in the ASsessment of the Safety and Efficacy of a New Thrombolytic agent (ASSENT-2) trial were evaluated to determine the feasibility of using the creatine kinase isoform method for comparison of two tissue-type plasminogen activators (tPA), recombinant tPA (r-tPA) and TNK-tPA. RESULTS: Early recanalization (within 40 min of the onset of treatment with the plasminogen activator) occurred in 56% of patients treated with r-tPA and 76% of those treated with TNK-tPA. CONCLUSIONS: Differences in the efficacy of plasminogen activators with respect to rapidity of recanalization appear to be readily detectable by means of assaying creatine kinase isoforms in serially acquired blood samples under conditions that permit widespread application of the approach developed.