OBJECTIVE We hypothesized that patients with more extensive coronary artery disease could be identified by abnormal left ventricular volume changes during dobutamine stress echocardiography. BACKGROUND In patients with more than one significant coronary artery stenosis, the typical hypercontractile function during dobutamine infusion may not occur. This may result in a smaller decrease or even an increase in left ventricular volumes at peak dobutamine infusion. METHODS We measured end-diastolic and end-systolic volumes in 61 patients undergoing dobutamine stress echocardiography and quantitative coronary analysis. Stress echocardiographic findings were positive in 39 patients (Group I) and negative in 22 (Group II). The percent change in these volume measurements from baseline to peak infusion were compared with quantitative coronary analysis jeopardy scores and incidence of two- or three-vessel coronary artery disease. An abnormal response was defined as < 15% decrease in end-diastolic or end-systolic volume. RESULTS Among the 39 patients with positive findings on dobutamine stress echocardiography (Group I), 11 had an abnormal end-diastolic volume response (< 15% decrease). Nine of these patients had two- or three-vessel coronary artery disease compared with 11 of 28 patients with a normal volume response (p < 0.05). In the 22 patients with negative findings on dobutamine stress echocardiography (Group II), an abnormal end-diastolic volume response was seen in 12 patients, 8 of whom had two- or three-vessel coronary artery disease, whereas none of the 10 patients with a normal volume response had two- or three-vessel coronary disease (p < 0.005; sensitivity 100%, specificity 68%). In the 12 patients with no significant coronary artery disease, end-diastolic and end-systolic volumes decreased by > 15% in all but 1. CONCLUSIONS Failure of end-diastolic volume to significantly decrease during dobutamine stress echocardiography identifies a group of patients with more extensive significant coronary artery disease.