The effects of therapy with essential amino acids and their nitrogen-free hydroxy and keto precursers on nitrogen and amino acid metabolism of patients with chronic renal failure were examined. Data obtained under treatment with essential amino acids and alpha-keto acid analogues showed higher levels of plasma amino acids, C3-complement, and transferrin than with a low-protein diet alone. Nitrogen balance became positive and plasma urea levels fell. With keto acid analogue therapy, these effects could be obtained with a reduced nitrogen intake. Supplementation of a low protein diet with alpha-hydroxy acid analogues was associated with more positive nitrogen balance and a rise in plasma histidine and methionine. However, plasma levels of three other essential amino acids fell.