The importance of timing of intravenous streptokinase (SK) administration in patients with acute myocardial infarction (AMI) was evaluated. Intravenous SK, 750,000 U, was administered within 4 hours of the onset of ischemic chest pain to 72 consecutive patients having their first AMI. Six days later, cardiac catheterization was performed to calculate global ejection fraction (EF), and computer-derived infarct-related regional EF and dysfunction index were also determined; electrocardiograms were recorded, from which QRS scores could be calculated to estimate infarct size. Of 19 patients who had an anterior AMI, 12 (63%) who received intravenous SK within 2 hours after onset of pain sustained only minimal damage in terms of global EF, infarct-related EF, dysfunction index and QRS score. All 10 patients who received SK 2 to 4 hours after pain onset had large infarcts (p less than 0.001). Of the former group, 11 of 12 patients (91%) whose pain was relieved within 1.5 hours of intravenous SK administration (presumably due to successful reperfusion) had a good outcome, whereas all 7 whose pain lasted longer did poorly (p less than 0.001). Furthermore, among patients with anterior AMI, 11 of 14 (79%) whose pain was relieved within 3.5 hours of onset had small infarcts, compared with none of the 12 patients whose pain lasted longer (p less than 0.0001). In inferior AMI, the critical time between onset of pain and initiation of intravenous SK was 1.5 hours (p less than 0.05). The timing of initiation of thrombolytic therapy and the total pain duration are critical in determining outcome in AMI, and time intervals vary depending on infarct localization.