At 9.5 mmoles/kg body weight, sodium benzoate sharply increased mortality in rats subsequently challenged with ammonia. Fasted animals were less sensitive to potentiation of ammonia toxicity by benzoate than were fed animals. At 2.5 mmoles/kg body weight, benzoate was observed to protect fasted animals against ammonia toxicity. Measurements of ammonia disappearance, urea formation, and hippurate synthesis in suspensions of isolated hepatocytes indicate that benzoate potentiates ammonia toxicity by inhibiting the urea cycle.