Forty-three consecutive patients with acute inferior transmural myocardial infarction but no history or electrocardiographic evidence of prior myocardial infarction were evaluated prospectively to assess the clinical and prognostic importance of persistent precordial (V1-V4) ST segment depression. Patients were evaluated within 24 hr of admission by history, physical examination, cardiac enzyme levels, right heart catheterization, and radionuclide angiography; all were followed for 1 year. Ten of the 43 patients (group I) had persistent anterior precordial ST segment depression, defined as 1 mm or greater in one or more precordial leads (V1-V2) 24 hr after admission to the coronary care unit, and 33 patients (group II) did not. Clinical variables that differed between groups I and II, respectively, included mean age (67 ± 9 [± 1 SD) vs 59 ± 8 years; p < .01), incidence of Killip class II to IV (100% vs 33%; p < .001), and average peak creatine kinase concentration (2878 ± 1139 vs 1511 ± 1034 IU/liter; p < .001). Hemodynamic differences between groups I and II included a higher pulmonary arterial wedge pressure (19 ± 4 vs 11 ± 5 mm Hg; p < .001) and a lower cardiac index (2.0 ± 0.5 vs 2.6 ± 0.7 liters/min/m2; p < .05). An evaluation of left ventricular ejection fraction and wall motion index by radionuclide angiography showed that group I had a lower ejection fraction (44 ± 11% vs 53 ± 10%; p < .05) and higher wall motion index (1.7 ± 0.4 vs 1.4 ± 0.3; p < .05) compared with group II. Prognostically, group I had a higher incidence of recurrent myocardial infarction (30% vs 0%; p < .01) and a higher 1 year mortality (60% vs 0%; p < .001). Univariate analysis revealed that several clinical, electrocardiographic, hemodynamic, and radionuclide angiographic variables were predictive of 1 year mortality, with persistent precordial ST segment depression being the most powerful (r = .73). Multivariate analysis was used to determine which variables had independent value for predicting death within 1 year. The most important variables were persistent precordial ST depression followed by elevated heart rate. No other variables added to this combination improved their predictive value (r = .82). We conclude that patients with their first acute inferior transmural myocardial infarction who have persistent precordial (V1-V4) St segment depression have clinical, hemodynamic, and noninvasive evidence of decreased left ventricular performance and a high 1 year mortality.