Patients with end-stage renal disease receiving chronic hemodialysis have impaired exercise tolerance. To distinguish between a central cardiorespiratory and a peripheral skeletal muscular origin for this fatigue, we measured exercise performance and peak oxygen consumption during a maximum exercise test in 10 patients receiving chronic hemodialysis. Skeletal muscle function was measured with an isokinetic cycle ergometer and a Cybex II isokinetic dynamometer. Peak rates of oxygen consumption (17.7 +/- 3.6 [mean +/- SD] mL O2/kg/min), blood lactate concentrations (3.4 +/- 0.9 mmol/L), peak heart rates (168 +/- 12 beats/min), and rates of ventilation (37.3 +/- 14.6 L/min) were low, but respiratory exchange ratios (1.1 +/- 0.1) were compatible with maximal effort. There was a significant correlation between isokinetic muscle strength and VO2 peak, exercise duration, peak ventilation, and peak blood lactate concentrations (P less than 0.05 to less than 0.001), but not between hemoglobin concentration, total blood hemoglobin content, or hematocrit and these variables. Therefore, in renal dialysis patients, isokinetic muscle strength is a better predictor of exercise capacity than are variables determining blood oxygen carrying capacity. This suggests that altered skeletal muscle function explains the impaired exercise tolerance of anemic patients with end-stage renal disease receiving chronic hemodialysis.