Since the area at risk for necrosis is the most important determinant of ultimate infarct size, knowledge of its size would be helpful in making therapeutic decisions during acute myocardial infarction. We hypothesized that indirect estimations of the risk area by use of clinical, electrocardiographic, hemodynamic, or angiographic variables are inaccurate in the setting of acute myocardial infarction. Accordingly, these variables were correlated with an echocardiographically derived risk area in 24 patients experiencing their first acute myocardial infarction. These patients underwent cardiac catheterization and echocardiography within 3 hours of hospital admission. The clinical (Killip class) and electrocardiographic findings (number of leads with ST segment changes) correlated poorly with the size of the risk area (r = 0.28 and r = -0.10, respectively). Hemodynamic data (which included right atrial, pulmonary artery, and pulmonary capillary wedge, aortic, and left ventricular end-diastolic pressures) and cardiac output, systemic and pulmonary vascular resistance, and heart rate demonstrated a poor correlation (r less than or equal to 0.47) with the risk area. The left ventricular ejection fraction and the number of diseased vessels determined by angiography also correlated poorly with the risk area (r = -0.47 and r = 0.10, respectively). Patients with multivessel disease were more likely to have abnormal wall motion remote from the infarct zone compared to patients with single-vessel disease (45% versus 8%, p less than 0.05). The left ventricular ejection fractions were lower in the group of patients with multivessel disease (0.43 versus 0.51, p = 0.06) and correlated better with the total extent of abnormal wall motion on echocardiography compared to patients with single-vessel disease (r = -0.67 versus r = -0.007). We conclude that clinical, electrocardiographic, hemodynamic, and angiographic variables do not provide an accurate estimate of the size of the left ventricular risk area during acute myocardial infarction. A direct visualization of left ventricular dynamics may provide a more accurate assessment of the size of the risk area and the total extent of left ventricular dysfunction.