A syndrome of dermatologic response to infection with phage Group 2 coagulase-positive staphylococci with reactions ranging from bullous impetigo to generalized scarlatiniform rash without exfoliation to generalized exfoliative disease was observed in 17 children. Staphylococci isolated from these patients, as well as two additional Group 2 organisms, produced exfoliation in newborn mice. The experimental lesion progressed from the development of a Nikolsky sign to bullous formation and then widespread exfoliation. Histologic sections were characterized by a cleavage plane within the epidermis at the stratum granulosum. Among 36 strains, the capacity to produce exfoliation was unique to staphylococci of phage Group 2. The disease produced in newborn mice reproduces the scalded-skin syndrome. Staphylococci may be recovered from involved animals. Thus Koch's postulates are fulfilled, and staphylococci of phage Group 2 are established as the etiologic agent of this syndrome.