Imaging of the right ventricle with 2-dimensional echocardiography (2-D echo) is hampered by trabeculation of the right ventricular (RV) endocardial surface and by limited echocardiographic resolution. Determination of RV ejection fraction (EF) is thus often an inconsistent and tedious procedure. The process of digital subtraction contrast echocardiography was developed to maximize echocardiographic definition of the right ventricle and to assess RVEF with minimal operator interaction. Videotaped 2-D echocardiograms recorded during i.v. injection of agitated saline were digitized. Masks were constructed from end-systolic and end-diastolic apical 4-chamber and parasternal RV short-axis images. Masks were subtracted from corresponding images recorded with contrast in the right ventricle; images of the contrast alone were extracted and their areas determined. EF was calculated from raw area measurements and after conversion to volume. Comparison with RVEF measured by first-pass radionuclide angiography yielded the following correlation coefficients: 4-chamber RV area, r = 0.79; parasternal short-axis RV area, r = 0.59; ellipsoid approximation RV volume, r = 0.84; pyramidal RV volume, r = 0.79; and Simpson's rule triangular cylinder RV volume, r = 0.62. Digital subtraction contrast echocardiography is a new method that can be used for semiautomated determination of RVEF. Further studies to assess the clinical values of digital image processing of 2-D echocardiograms to measure RV function appear warranted.