Staphylococcal scalded skin syndrome (SSSS) is primarily a disease of neonates, young children and immunocompromised adults, characterized by infection with exotoxin, exfoliative toxin A (ETA) or B (ETB), producing Staphylococcus aureus. A murine model closely resembles human SSSS in age differentiation and pathology. ETA was reported to possess superantigenic activity, but subsequent studies with a recombinant toxin failed to reproduce this activity. To address the biological and possible immunological aspects of the apparent differences in pathogenicity of this organism in the neonatal population versus the adult population, we investigated whether recombinant ETA (rETA) would function as a superantigen in the neonatal population. The ETA encoding gene was isolated using PCR techniques, and inserted into an Escherichia coli expression system for isolation and purification of the toxin. Purified rETA was tested for activity in the neonatal mouse model. The neonatal mice showed symptoms of exfoliation in a dose dependent manner confirming the activity of the recombinant toxin. rETA was analyzed for superantigen activity in standard mitogenicity assays using adult peripheral blood mononuclear cells and umbilical cord blood as a source of neonatal mononuclear cells. The known superantigen SpeA (streptococcal pyrogenic exotoxin A) was used as a positive control. Recombinant ETA did not have superantigen activity in this assay. These studies support the conclusion that rETA does not function as a superantigen in either the adult or neonatal population but does not rule out an immunological component to explain the difference in the pathogenesis of SSSS in the neonate versus the adult. Investigations are currently underway to address the possible roles of T and B cells utilizing B cell mutant mouse populations and T cell depleted mice. Current studies are also in progress to address the structure and function of ETA.