A 3-week-old septicemic full-term infant developed severe metabolic acidosis (total CO2 < 5 mEq/l) and underwent intravenous antibiotic and bicarbonate therapy with good response. Attempts to introduce milk formulae triggered recurrence of metabolic acidosis (total CO2 < 11 mEq/l) which was spontaneously corrected without bicarbonate therapy during periods when only glucose and water or PM 60/40 were given. One month after apparent recovery from the septicemia, the technique of net acid balance was applied to study the effects of Nutramigen on each component of endogenous net acid production and net acid excretion. Comparison was made with similar balance periods on glucose-water and Similac formulae. When metabolic acidosis developed during feedings on Nutramigen and Similac, the acid balance was positive. Spontaneous recovery occurred when glucosewater was substituted and acid balance reverted to zero.The data indicated that the acidogenic properties of Nutramigen and Similac played an important part in the development of acidosis; whereas, glucose-water was shown to be compatible with zero to negative hydrogen ion balance and recovery from systemic acidosis. It was postulated that as a sequelae of the septicemia, the renal acidification mechanism was temporary impaired, resulting in the development of metabolic acidosis when the milk formulae with greater hydrogen ion loads were used. It was recommended that, besides correction with sodium bicarbonate, substitution of milk formula with glucose-water for a few days should be considered in infants who develop systemic acidosis without apparent cause.