We compared computer-enhanced digital angiography (CEDA) following pulmonary injection of 20 ml Renografin-76 (5 ml/sec) to conventional directly injected left ventriculography (LV) in 13 patients undergoing routine diagnostic catheterization. Left ventricular ejection fraction (LVEF) was determined by planimetry from end-diastolic and end-systolic images by two independent angiographers. The correlation coefficient for LVEF (CEDA vs. LV) was r = 0.75 (p less than 0.005) for observer 1 and r = 0.85 (p less than 0.0005) for observer 2. The interobserver variability for LVEF was very low, resulting in a high correlation coefficient (r = 0.91, p less than 0.0005). Three angiographers independently reviewed both the conventional and CEDA images in a random order for assessment of anterior, apical, and inferior regional wall motion, using a 6-point subjective grading system (198 determinations). The interobserver correlation for subjective assessment of regional wall motion by both LV and CEDA was poor (49% for LV and 59% for CEDA, p = NS). These poor correlations were not improved by excluding any region or angiographer from the analysis. The agreement of regional motion assessments between the two techniques was only 40%. To improve reproducibility of wall motion interpretation, an automated analysis program was developed. First the range of normal contraction was defined from pooled literature data. The movement of any segment of the left ventricular wall could then be determined in millimeters and referenced to the normal range. This method eliminated interobserver variability. In the absence of an acceptable standard of segmental wall motion to which this measurement can be compared, the accuracy of this objective format could not be determined. We conclude that CEDA images allow accurate determination of ejection fraction and that the large interobserver variability of subjective regional wall motion analysis can be overcome by employing more objective formats.