The relative effectiveness of exchange transfusion, peritoneal dialysis, arginine, and sodium benzoate was evaluated during 44 episodes of hyperammonemic coma in 31 patients with congenital urea cycle enzymopathies. The overall survival rate was 56%. In 15 episodes treated with EXT the fall in ammonium was 19 +/- 24%, P > 0.05. In 30 episodes treated with PD, the fall in ammonium was 60 +/- 9%, P < 0.001. Ten times more nitrogen was removed as glutamine than as ammonium during dialysis, suggesting that the effectiveness of PD resides in the removal of glutamine, glutamate, and alanine as well as ammonium. Prior to therapy all patients had hypoargininemia (18 +/- 2 microM); they responded to arginine supplementation with a rise in plasma arginine concentration to normal. In patients with AL deficiency, arginine supplementation (4 mmol/kg/day) was associated with a fall in ammonium level from 917 +/- 62 to 103 +/- 18 microM within 24 hours. When sodium benzoate (250 mg/kg/day) was used during eight episodes of coma, six patients responded with a significant decrease in plasma ammonium.