The clinicopathological syndrome of kernicterus observed in rats with congenital hypoglucuronyltransferasia (Gunn's strain of rats) is similar to the syndrome of human kernicterus. The earliest detectable changes in ganglion cells are associated with the presence of intracellular bilirubin. Sulfonamides, do not produce kernicterus in normal newborn rats, nor do they alter the blood-brain barrier. Their deleterious effect in Gunn's strain of rats and in premature infants may be explained by the displacement of bilirubin from the blood compartment into the extracellular fluid. It is suggested that a similar mechanism may be operative in kernicterus occurring under other circumstances. The toxic unconjugated bilirubin is probably the cause of central nervous system damage.