To investigate the mechanisms and clinical significance of precordial (V1-V4) ST segment depression during acute inferior myocardial infarction, stress thallium-201 scintigrams and coronary angiograms were obtained within four to eight weeks after the onset of myocardial infarction in 37 patients experiencing their first acute inferior myocardial infarction. Among 18 patients with precordial ST depression (group 1), 11 with concomitant disease of the left anterior descending artery (LAD) had positive results on exercise test, whereas in seven patients without LAD lesion, only two had positive exercise test (p less than 0.01). In 19 patients without precordial ST depression (group 2), 11 had severe stenosis in the LAD. However, among these 11 patients, only two had positive exercise tests. Patients with precordial ST depression demonstrated a higher frequency of positive exercise tests than those without it (p less than 0.01). On stress thallium-201 scintigraphy, a perfusion defect involving the inferior wall was present in all patients, but additional anterior wall ischemia was present in only five of the 18 patients in group 1. These five patients had chest pain on exercise tests and a severe stenosis greater than 90% in the LAD. There was no significant difference in the frequency of additional posterolateral wall infarction between groups 1 and 2. In 18 patients in group 1, sigma ST (total degrees of ST segment depression in leads V1, V2, V3, and V4 in the acute stage) was significantly greater in 11 patients with LAD lesion than in seven without (p less than 0.05), and sigma ST greater than five mm was observed in 12 of 13 patients who had additional anterior wall ischemia and posterolateral wall infarction on stress thallium-201 scintigraphy (p less than 0.05). Myocardial revascularization, such as aortocoronary bypass surgery or percutaneous transluminal coronary angioplasty (PTCA), was performed in six of the 18 patients in group 1 in the chronic stage, but in only one of the 19 patients in group 2. Thus, in patients with initial acute inferior myocardial infarction, those with precordial ST depression seemed to be a high-risk group. It was suggested that, during the early stage of myocardial infarction, this abnormality on electrocardiograms is related to the summation of effects of anterior wall ischemia and posterolateral wall infarction. Furthermore, the sigma ST evaluation is useful in differentiating a mirror image of inferior wall infarction from anterior wall ischemia and posterolateral wall infarction as the mechanism of precordial ST depression.