To study the mechanism and prognostic importance of precordial ST-segment depression during inferior acute myocardial infarction, 162 patients admitted during 1969 through 1982 were identified. Patients with ST depression in leads V1, V2 and V3 had significantly larger infarctions as assessed by a QRS scoring system. Hospital mortality was 4% (3 of 75) among patients without ST depression, and 13% (11 of 87) in patients with ST depression. The relation between the amount of ST depression and hospital mortality was significant (p less than 0.001 by logistic regression), and remained significant (p less than 0.003) after adjusting for other potentially prognostic factors. Among patients discharged from the hospital, the 5-year survival was 92% in those without precordial ST depression and 80% in those with precordial ST depression (p = 0.058 by the Cox model). Precordial ST-segment depression on the admission electrocardiogram during an inferior acute myocardial infarction indicates a larger infarction, predicts a higher hospital mortality and suggests a worse long-term prognosis after discharge.