In normal subjects, short to intermediate responses to dietary protein restriction include decreased amino acid oxidation and protein degradation plus increased utilization of amino acids for protein synthesis; these responses are activated to improve amino acid utilization and nitrogen balance. To assess whether chronic renal failure (CRF) impairs the adaptive responses to a low-protein diet, we measured nitrogen balance and the kinetics of infused L-(15N,1-13C)leucine during fasting and feeding. In six adult CRF and four control (C) subjects, 0.6 (LP) and 1.0 (HP) g protein kg-1 day-1 diets were compared. LP reduced feeding stimulated oxidation of leucine by 26% in CRF and 33% in C (P = NS). During fasting, oxidation was unaffected by diet or CRF. For both groups, feeding suppressed protein degradation to the same extent; leucine incorporation into protein did not change. Nitrogen balance during the two diets was the same with C and CRF, as was protein balance estimated from results of measured leucine kinetics. Thus, patients with CRF can activate appropriate adaptive responses to LP inasmuch as reduced amino acid oxidation occurring with feeding and estimates of protein balance did not differ from control.