Impaired exercise tolerance, determined by peak oxygen consumption ((V)ovr dot O-2 peak), is predictive of mortality and the necessity for cardiac transplantation in patients with chronic heart failure (HF). However, the role of left ventricular (LV) diastolic function at rest, reflected by chamber stiffness assessed echocardiographically, as a determinant of exercise tolerance is unknown. Increased LV chamber stiffness and limitation of (V)over dot O-2 peak are known correlates of HF. Yet, the relationship between chamber stiffness and (V)over dot O-2 peak in subjects with HF has not been fully determined. Forty-one patients with HF New York Heart Association [(NYHA) class 2.4 +/- 0.8, mean +/- SD] had echocardiographic studies and (V)over dot O-2 peak measurements. Transmitral Doppler E waves were analyzed using a previously validated method to determine k, the LV chamber stiffness parameter. Multiple linear regression analysis of (V)ovr dot O-2 peak variance indicated that LV chamber stiffness k (r(2) = 0.55) and NYHA classification (r(2) = 0.43) were its best independent predictors and when taken together account for 59% of the variability in (V)ovr dot O-2 peak. We conclude that diastolic function at rest, as manifested by chamber stiffness, is a major determinant of maximal exercise capacity in HF.