Patients with varying degrees of renal failure were studied for their blood lactate response to exercise on either a treadmill or a bicycle ergometer. In the group exercised on a treadmill, blood lactate and alanine levels were measured, and in the group exercised on the bicycle ergometer blood lactate levels and oxygen uptake were measured. In both groups regardless of the method of exercise or the degree of azotemia, a rapid rise in blood lactate similar to that previously reported with exercise was observed. Blood alanine levels, which were low in subjects with renal disease, did not change with exercise even with a rise in blood lactate levels. There was no difference in the oxygen uptake between normal controls and subjects with renal disease. We conclude that blood alanine levels are low in renal disease, and that with the degree of exercise studied the rise in blood lactate in patients with renal disease is not accompanied by a change in oxygen uptake and does not evoke a rise in blood alanine levels. The mechanisms for the abnormal rise in blood lactate in these patients does not appear to be due to anoxia.