Twelve patients with severe chronic renal failure (average initial GFR, 13 mL/min) were monitored for 4 to 23 months while receiving an essential amino acid supplement and were then switched to a ketoacid supplement for 6 to 40 months, while continuously receiving a very low-protein (0.3 g/kg), low-phosphorus (7 to 9 mg/kg) diet. Urinary urea N excretion indicated that actual dietary protein intake averaged 0.46 g/kg. Progression, estimated as the linear regression slope of radioisotopically determined GFR on time, slowed from -0.46 +/- 0.31 (SD) to -0.24 +/- 0.15 mL/min/month (P = 0.029). Serum urea N, creatinine, phosphate, and uric acid rose significantly as GFR fell; blood pressure, plasma lipids, and urinary urea excretion were unchanged. Urinary 17-hydroxy-corticosteroid excretion decreased 18%, but this change was only marginally significant (P = 0.087). There was no change in plasma or urinary cortisol or urinary aldosterone. Viewed in light of previous evidence that progression seldom slows when treatment remains constant, the results suggest that this ketoacid supplement slows progression by approximately half, compared with an essential amino acid supplement, with no change in diet.