To investigate the influence of thrombolytic therapy on the natural history of left ventricular size and regional function after myocardial infarction, 32 patients treated with acute thrombolytic therapy (treatment group) were studied by echocardiography on admission to the hospital and at 1 week, 3 months, and 1 year after myocardial infarction; they were compared with 40 patients who did not receive acute intervention (control group). The endocardial surface area index (cm2/m2) and the area of abnormal wall motion (cm2) were calculated from left ventricular dimensions and measurements of abnormal wall motion. Although no differences in the endocardial surface area index were noted over the year for the groups as a whole, a significant difference was noted in treated anterior infarctions with early functional infarct expansion compared with untreated infarct expansion (treatment group: 85.8 +/- 2.0 cm2/m2 [entry] to 77.4 +/- 2.7 cm2/m2 [1 week] to 69.9 +/- 4.2 cm2/m2 [3 months] to 67.2 +/- 6.4 cm2/m2 [1 year] versus control group: 84.0 +/- 6.4 cm2/m2 [entry] to 83.7 +/- 8.5 cm2/m2 [1 week] to 96.3 +/- 8.6 cm2/m2 [3 months] to 81.5 +/- 4.2 cm2/m2 [1 year]; p < 0.01). When early expansion was present, those receiving thrombolysis exhibited a consistent decrease in the initially enlarged endocardial surface area in contrast to control subjects, who demonstrated continued increases in endocardial surface area during the first 3 months. In all groups a decrease in the area of abnormal wall motion was observed during the year of follow-up. However, the magnitude and timing of the improvement was accelerated in the treatment group. Thus acute thrombolytic therapy alters the natural history of left ventricular size and function with a more rapid recovery of abnormal endocardial segments and reversal of functional infarct expansion.