Combined two-dimensional and Doppler echocardiography has a high sensitivity and specificity for detection of isolated perimembranous ventricular septal defects. However, muscular or multiple ventricular septal defects may be difficult to diagnose with noninvasive methods, particularly in older children, necessitating angiography for accurate diagnosis. Detection of single and multiple ventricular septal defects with two-dimensional color flow mapping was compared with detection by standard two-dimensional imaging and Doppler. Both techniques were compared with four-chamber left ventricular angiography. Fifty-one patients (age 3 months to 25 years, mean 5.6 years) were studied. Eighteen had solitary ventricular septal defects, 18 had multiple ventricular septal defects, and 15 patients with intact ventricular septum served as a control group. At least one ventricular septal defect was detected by color Doppler and two-dimensional/Doppler methods in all patients with ventricular septal defect proved by angiography with no false positives. In the detection of multiple ventricular septal defects, the sensitivity of color Doppler was 72% and that of two-dimensional/Doppler was 38% (100% specificity in both). Color Doppler failed to identify multiple ventricular septal defects in five patients (two weighing less than 4 kg and three with reduced pulmonary blood flow). However, no large additional muscular defects were missed by imaging and color Doppler. Color Doppler is useful for the detection of ventricular septal defects and has higher sensitivity than two-dimensional/Doppler for multiple ventricular septal defects. The contribution of color Doppler appears to be in the detection of additional small muscular ventricular septal defects.