To investigate how uremia modified by maintenance hemodialysis treatment influences the extra- and intracellular amino acid pattern, we collected muscle samples by percutaneous muscle biopsy and plasma samples for determination of free amino acids in 11 functionally anephric patients (creatinine clearance less than 1 ml/min), who had been treated with hemodialysis for greater than 6 months and had no clinical or laboratory signs of protein malnutrition. Five patients had mild acidosis (standard bicarbonate pre-dialysis 18 to 21 mmol/liter). The amino acid results were compared with data from age- and sex-matched healthy controls and with data obtained earlier from non-dialyzed patients with chronic uremia. In the hemodialysis patients threonine, serine and valine were significantly reduced in plasma compared to the controls, whereas the plasma concentrations of aspartate, glycine, citrulline, cysteine and arginine were elevated. In aspartate, glycine, citrulline, cysteine and arginine were elevated. In muscle, valine, serine and the tyrosine to phenylalanine ratio were low. Compared with the untreated uremic patients the hemodialysis patients exhibited fewer significant abnormalities, but the general pattern was similar, demonstrating that hemodialysis is unable to fully correct the amino acid abnormalities of chronic uremia. There was a significant positive correlation between both pre-dialysis and post-dialysis plasma bicarbonate and the muscle valine concentration, suggesting that mild acidosis may be causally related to the inbalance of the branched-chain amino acids in uremia. Extra- and intracellular serine depletion in the presence of high plasma glycine may reflect a defect in the metabolism of glycine to serine in hemodialysis patients, related to a lack of metabolizing renal tissue.