Severe transient hyperammonemia is a disorder of unknown etiology which can be successfully treated. This article describes two infants affected by this condition and reviews the pertinent literature. Forty-nine cases, including our own, are summarized. Large prematures (mean birthweight 2534 +/- 738 gm, gestational age 36.1 +/- 4.05 weeks) and infant males most commonly were affected. The peak plasma ammonium concentration did not discriminate between infants who lived and those who died, underscoring the need for aggressive therapy regardless of the initial plasma ammonium concentration. Abnormal liver enzymes were reported in seven cases. Most of these infants were asphyxiated at birth. Exchange transfusions (ET), alone or in combination with peritoneal dialysis, was the most common form of therapy. Of the infants treated with this therapy, 83% survived. Sixty-six percent of the survivors, for which data are available, were normal on follow-up examination. It is not known at present to what extent the associated peritoneal asphyxia was responsible for the observed neurologic sequelae. Increased awareness of this condition and the choice of hemodialysis as a form of therapy may further reduce both morbidity and mortality.