15N-glycine administered orally to 3 patients with chronic renal failure and 15N-ammonium chloride given by intravenous infusion to 5 patients were used as tracers in studying the total body nitrogen metabolism during the course of dietary therapy. Patients on a diet providing 1.2 g protein per kilogram body weight per day had significantly lowered total nitrogen flux (Q) and rates of total body protein synthesis (S) and catabolism (C) as compared with the normal controls. A reduction in daily protein intake to 0.6 g/kg/day resulted in marked increases in all these parameters, so that the values actually approached that of the normal controls. While in the normal subjects low-protein intake did not affect the total body protein turnover significantly, it tended to decrease Q and to raise S, C, and S/Q. The results of the present study suggest that the adaptive response to restriction in protein intake is a more efficient utilization of nitrogen entering the metabolic pool for anabolic purposes, and less nitrogen excreted as urea. This response becomes manifest and essential to patients with chronic renal failure and forms the basis for low-protein diet therapy.