The rapid development of numerous therapeutic options for myocardial revascularization requires more advanced, quantitative echocardiographic methods such as measurement of total endocardial and infarct surface area to evaluate myocardial infarction and assess the effects of therapy. Two-dimensional echocardiography is insufficiently quantitative for this purpose because it cannot directly measure three-dimensional relationships with such as volume and surface area. To limitation this limitation we have developed a three-dimensional echocardiograph capable of measuring total and regional or "infarct" surface area. In vitro validation of this method has been carried out comparing computed areas with true areas of a pin model and fixed hearts. Infarcts were demarcated on the fixed hearts by placing pins in the myocardium. The pin heads on the epicardial surface defined infarct regions that could be imaged. True surface areas of the pin model were determined by physical measurement and calculation. True areas of the fixed hearts were determined by planimetry of surface casts made with plastic tape. Accuracies for total and infarct areas were 1.36% and 2.13% for the pin model and 1.61% and 3.48% for the fixed hearts. Interobserver variability for both phantoms was less than 2.5%. The standard error of the estimate predicting total and infarct surface area for the fixed hearts was 1.53 cm2 and 0.71 cm2, respectively (p < 0.001). Three-dimensional echocardiography provides a new, accurate method for directly measuring global and regional surface areas and holds promise for improved evaluation of myocardial infarction and assessment of its treatment.