Skeletal muscle protein synthesis and degradation in patients with chronic renal failure. Muscle protein turnover and amino acid (AA) exchange across the forearm were studied in nine postabsorptive patients with chronic renal failure (CRF) under unrestricted calorie-protein diets and eight controls by using the arterio-venous difference technique associated with the 3H-phenylalanine kinetics. In patients with CRF: (1) the rate of appearance (Ra) of phenylalanine (Phe) from the forearm, reflecting proteolysis, was 27% increased in comparison with controls (P < 0.01). Also the rate of disposal (Rd) of Phe, reflecting protein synthesis, was increased in patients (P < 0.01). As a consequence of these counterbalanced alterations, net balance of Phe across the forearm, that is, net proteolysis, was not changed. (2) The release of total AA from the forearm was not different from controls. Valine and ketoisocaproate release was reduced (P < 0.05). Serine uptake was not detectable. (3) Net proteolysis and the Rd/Ra ratio were inversely and directly, respectively, related to arterial [HCO3-] (P < 0.02 and P < 0.03, respectively). (4) Moreover, net proteolysis and Phe Rd/Ra ratio were directly and inversely, respectively, correlated with plasma cortisol (P < 0.01 and < 0.005, respectively). Plasma cortisol was in the normal range and inversely related to arterial [HCO3-] (P < 0.02). (5) While in controls phenylalanine appearance from the forearm was inversely related to insulin levels, no correlation was found in patients. In conclusion, in patients with CRF, forearm Phe kinetics indicate the existence of an increased muscle protein turnover. Changes in protein synthesis and degradation are well balanced and net proteolysis is not augmented. However, net proteolysis increases in proportion to the degree of metabolic acidosis because protein synthesis rises less than protein breakdown. Variations in net proteolysis are best accounted for by changes in plasma cortisol levels, suggesting that cortisol plays an important role in variations in muscle net proteolysis in patients with CRF and metabolic acidosis. A resistance of muscle proteolysis to basal insulin levels likely takes place.