Precordial ST-segment depression (PSD) in inferior wall acute myocardial infarction (IAMI), especially when maximal in leads V4-V6, has been shown to portend a higher rate of heart failure and mortality. To better understand the pathophysiology behind this phenomenon, we evaluated patients with a first IAMI by echocardiography 48-72 h after the acute event, using segmental scoring (0 = normal to 3 = dyskinesia) of left ventricle wall motion, and a dichotomous assessment of right ventricle involvement. Patients were categorized into 3 groups: I = no PSD (n = 14); II = maximal PSD in leads V1-V3 (n = 28); III = maximal PSD in leads V4-V6 (n = 8). As compared with group I, patients in groups II-III had more severe wall motion abnormalities in inferior segments (1.36 +/- 0.97 vs. 2.19 +/- 1.74, p = 0.04), and a similar trend for posterior and lateral segments (1 +/- 1.75 vs. 2 +/- 2.41, p = 0.11), translating into a worse total left ventricle score (2.36 +/- 2.34 vs. 4.25 +/- 4.05, p < 0.05). Frequency of right ventricle involvement was similar in patients with and without PSD (6 (43%) vs. 9 (25%), p = 0.37). Segmental scores for groups I, II, and III, respectively, were not different for inferior (1.36 +/- 1, 2.25 +/- 1.82 and 2 +/- 1.51, p = 0.24), posterior and lateral (1 +/- 1.75, 1.96 +/- 2.32 and 2.13 +/- 2.9, p = 0.38), and septal, anteroseptal and anterior segments (0 +/- 0, 0.04 +/- 0.19 and 0.13 +/- 0.35, p = 0.28). Right ventricle abnormalities occurred in 43, 21 and 38% of patients in groups I, II and III, respectively, p = 0.3. Thus, IAMI with PSD is associated with worse left ventricle wall motion. However, since patients with maximal PSD in leads V4-V6 do not have greater wall motion abnormalities or higher rate of right ventricle involvement, their poorer prognosis cannot be explained by worse systolic dysfunction. We propose that maximal PSD in leads V4-V6 reflects transient diffuse ischemia and altered diastolic distensibility due to extensive coronary artery disease, causing increased left ventricle end-diastolic pressure.