1. The possibility that abnormalities of skeletal muscle may limit the exercise tolerance of patients with chronic renal failure was investigated in patients undergoing regular haemodialysis. 2. Blood flow to the calf, a vascular bed consisting predominantly of skeletal muscle, was measured in six patients before and after exercise and compared with values obtained from 12 control subjects. 3. The patients were limited on exertion and had an abnormal response of calf blood flow to bicycle exercise. Resting calf blood flow was similar in patients and control subjects, but the mean increase in calf blood flow in response to submaximal exercise was 0.55 (sem 0.12) ml min −-1 100 ml −-1 in the patients and 1.43 (sem 0.17) ml min −-1 100 ml −-1 in the control subjects. The increase after symptom-limited maximal exercise was 1.50 (sem 0.80) ml min −-1 100 ml −-1 in the patients and 4.20 (sem 0.40) ml min −-1 100 ml −-1 in the control subjects. 4. Skeletal muscle biopsies from eight haemodialysis patients were studied by histochemistry and electron microscopy. 5. Oxidative enzyme activity was increased and there were large subsarcolemmal aggregates of structurally normal mitochondria. Necrotic capillaries were observed as empty basement membrane tubes containing fragments of degenerating endothelium. 6. The changes were compatible with a response to a chronic reduction in skeletal muscle blood flow.