Early noninvasive detection of reperfusion after thrombolysis for acute myocardial infarction may enable detection of unsuccessful thrombolysis in time for rescue percutaneous transluminal coronary angioplasty (PTCA). It has been suggested that repeated measurement of myoglobin or of MM creatine kinase (CK) isoforms enables early detection of reperfusion. Twenty consecutive patients with acute myocardial infarction treated by intravenous thrombolysis underwent serial determination of myoglobin, MM3 and MM1 CK isoforms every 30 minutes after the beginning of thrombolysis. At 90 minutes, coronary angiography was performed, enabling classification of patients as with (group A) and without (group B) reperfusion. A third group of 7 patients (group C) underwent direct PTCA without antecedent thrombolysis. In all groups, there were increases in myoglobin, percentage of MM3 isoform, and ratio of MM3/MM1. These increases appeared on the average steeper and faster in group B, but the large dispersion of values in this group resulted in a wide overlap with group A. Retrospective analysis suggests that an increase in the MM3/MM1 ratio > 0.35 after 60 minutes is very specific for reperfusion (sensitivity 60% and specificity 100%). In group C, PTCA always led to a sharp increase in all biochemical parameters measured within 30 minutes. Thus, macromolecular markers can be used for very early, noninvasive detection of reperfusion with a high specificity. This could help reduce the need for emergency angiography to select candidates for rescue PTCA. Furthermore, the patterns of biochemical markers of reperfusion differ when reperfusion is initiated by either thrombolysis or PTCA.