Densitometric regional ejection fraction obtained by computer analysis of digital subtraction ventriculography was evaluated as a new, quantitative, three-dimensional index of regional left ventricular performance. Eighteen patients with coronary artery disease and seven control subjects had right anterior oblique ventriculography at rest and immediately after rapid atrial pacing using central venous injection of contrast material. Regional left ventricular ejection fraction was determined by densitometry in six segments drawn around the end-diastolic center of gravity, and compared with two conventional indexes of segmental wall motion: area and radial regional ejection fraction. Densitometric, area or radial regional ejection fraction was classified as abnormal if it fell at least 2 standard deviations below the corresponding mean value in the normal group. The densitometric method did not require outlining of the end-systolic left ventricular silhouette and was the easiest and fastest to perform of all three techniques. In addition, intra- and interobserver reproducibilities were higher with the densitometric method (r = 0.97 and 0.95) than with either the area (r = 0.84 and 0.82) or the radial method (r = 0.82 and 0.76). Regional left ventricular dysfunction as assessed by the densitometric, area and radial techniques allowed the detection of coronary artery disease in 50, 50 and 44% of the patients at rest and in 83, 67 and 61% of the patients in the post-pacing period, respectively. Post-pacing regional left ventricular dysfunction accurately predicted the presence or absence of greater than 70% diameter stenosis in the supplying coronary artery in 75, 67 and 56% of the cases, respectively. Thus, densitometric analysis of digital subtraction ventriculography allows a fast and reproducible three-dimensional determination of regional left ventricular ejection fraction. Using this technique, pacing-induced regional dysfunction can be detected in most patients with coronary artery disease and corresponds well with the location of significant coronary artery lesions.