Existing studies suggest that exercise-induced ischemia produces an increase in left ventricular end-diastolic volume; however, all of these studies have included patients with previous myocardial infarction. To test whether the end-diastolic volume response to exercise is related to the extent of myocardial scar, the results of gated radionuclide supine exercise tests performed on 130 subjects were reviewed. The patient group comprised 130 men aged 35 to 65 years (mean ± SD 52 ± 5) with documented coronary heart disease. The extent of myocardial ischemia and scar formation was assessed by stress electrocardiography and thallium-201 scintigraphy. Patients were classified into three groups on the basis of left ventricular end-diastolic volume response at peak exercise: group 1 (n = 72) had an increase of end-diastolic volume greater than 10%, group 2 (n = 41) had a change in end-diastolic volume less than 10% and group 3 (n = 17) had a decrease in end-diastolic volume greater than 10% (n = 17). At rest there was no significant difference among groups in heart rate, systolic blood pressure, end-diastolic (EDVrest) or end-systolic volumes or ejection fraction (p > 0.05); however, at peak exercise the end-systolic volume response was significantly greater for group 1 (p < 0.002). Analysis of variance revealed no significant difference (p > 0.05) in the extent of exercise-induced lateral ST segment depression among group 1 (−1.24 ± 1.1 mV), group 2 (−0.91 ± 1.0 mV) or group 3 (−0.75 ± 0.9 mV), or the thallium-201 “ischemia scores” among group 1 (4.1 ± 4.5), group 2(3.4 ± 4.1) or group 3 (2.5 ± 2.8). Thallium-201 “scar scores” (SCAR), however, were significantly different (p < 0.01) among the three groups 13.9 ± 7.1, 10.6 ± 6.7 and 9.5 ± 4.8, respectively. Multivariate linear regression analysis indicated that the percent change in end-diastolic volume (%EDV) was best described by the equation: %EDV = 1.5[scar] −0.22[peak systolic blood pressure] −0.29[EDVrest] + 81.6 (r = 0.49, p < 0.0001). These data suggest that in men, exercise-induced changes in end-diastolic volume during supine exercise are related to the extent of myocardial scar.