Nine patients with severe chronic renal failure (mean glomerular filtration rate 4.8 ml/min; mean serum creatinine 11.3 mg/dl) who were previously on a protein-restricted diet were treated with a diet containing an average of 33 kcal/kg and 22.5 g/day of mixed quality protein, supplemented by a combination of amino acids and mixed salts formed between basic amino acids and keto-analogues of essential amino acids. The supplement was designed to minimize or reverse the amino acid abnormalities of chronic renal failure rather than to meet the normal requirements for the essential amino acids; it contained tyrosine, ornithine, and a high proportion of branched-chain ketoacids, but no phenylalanine or tryptophan and very little methionine. Within one month, serum urea nitrogen fell and serum albumin and transferrin rose significantly; serum creatinine fell slightly. Hyperphosphatemia (present in three patients) was corrected. Nitrogen balance, measured in seven of the nine patients, on the average was neutral, as it was in a preceding control period on a 40 to 50 g/day protein diet. Plasma tyrosine and threonine, which were subnormal before therapy, rose to normal or high normal levels. Branched-chain amino acids did not change. During a total of 63 patient-months of therapy, no side effects or toxicity were observed, and serum albumin and transferrin did not change further. It is concluded that this specially designed supplement added to a 20 to 25 g/d protein diet is an acceptable regimen which can improve or maintain protein nutrition in patients with severe chronic renal failure who would otherwise require dialysis.