To determine if cause influences the left ventricular (LV) volume and ejection fraction (EF) response to exercise, 24 patients with chronic congestive heart failure (CHF) (13 dilated cadiomyopathy [DC], CHF-DC group; 11 previous myocardial infarction [MI], CHF-MI group) and 6 age-matched control subjects underwent simultaneous hemodynamic monitoring and radionuclide ventriculography during semiupright bicycle exercise. Both CHF groups had similar hemodynamic values, LV volumes and EF at rest. Exercise hemodynamics were also similar, but LV volume and EF responses to exercise were different. In the CHF-DC group LV end-diastolic volume increased by 15% during exercise, significantly less (p < 0.01) than the 44% increase in CHF-MI group. During exercise, EF increased in CHF-DC group, but did not change in CHF-MI group because of a larger increase in end-systolic volume. The slope of mean pulmonary wedge pressure-LV end-diastolic volume relation was steeper in CHF-DC group than in CHF-MI group (p < 0.01). The study suggests that LV volume and EF response to exercise in patients with CHF depends on the origin of the CHF.