The distribution and excretion of the staphylococcal exfoliatin was investigated following in vivo administration of highly purified ¹²⁵I‐labelled exfoliatin fractions to adult and newborn mice. Adult mice excrete approximately one‐third of a test dose by 3 hours as compared to a fifteenth of a test dose excreted by newborn mice. Accordingly, blood tracer radioactivity reaches a relatively higher peak and shows a slower decline in newborns than in adults. The urine of adult mice contains considerable biologically active exfoliating material. Both nephrectomized and carbon tetrachloride‐poisoned adult mice injected with exfoliatin develop generalized exfoliation whereas comparable doses in untreated controls have no effect. On the other hand, subtotal hepatectomy, followed by injection of exfoliatin, does not lead to exfoliation. We conclude that renal immaturity is a critical factor responsible for the susceptibility of neonates to generalized staphylococcal scalded skin syndrome.