It is currently unknown if metabolic acidosis has any effect on muscle protein metabolism in patients with chronic renal failure (CRF). To address this question, muscle protein turnover was studied in patients with CRF and controls in the postabsorptive state by using the forearm perfusion method together with the 3H-phenylalanine kinetics. Nine patients were acidotic ([HCO-3]a = 20 +/- 0.5 mEq/l) whereas 4 patients had a normal acid-base balance ([HCO-3]a = 25 +/- 0.3 mEq/l). In patients with metabolic acidosis the rates of phenylalanine appearance and disposal from the forearm were increased as compared to controls. Phenylalanine net balance, i.e. net proteolysis, was only slightly higher than in controls. In patients under a normal acid-base balance both rates of appearance and disposal of phenylalanine as well as phenylalanine net balance were similar to controls. These preliminary data suggest that metabolic acidosis can enhance the rate of muscle protein degradation in patients with CRF.