Latex allergic health care workers are exposed to numerous chemicals in addition to natural rubber latex (NRL) proteins. Time course studies have demonstrated a dose responsive increase in total and NRL specific serum IgE levels in female BALB/c mice exposed to 25 ug NRL and increasing concentrations of glutaraldehyde from 0.05ppm 1 % (doses surrounding the recommended PEL). These studies investigated the mechanistic basis underlying the immunomodulation of the IgE response to NRL proteins following concurrent glutaraldehyde exposure. Using in vitro flow through cells and skin from hairless guinea pigs, penetration studies demonstrated no significant increases in NRL protein penetration through skin from animals that had been exposed dermally to 0.75 ppm glutaraldehyde 5 days a week for up to 56 days. Immunohistochemical staining of epidermal sheets demonstrated up regulation of MHC class II expression following 3 days of exposure to glutaraldehyde. No significant increase in MHC class II expression was observed in lymph node cells from animals exposed to NRL alone. Ten days following co-exposure to glutaraldehyde and NRL proteins, an increase in MHC class II expression (>45%) was observed in lymph node cells draining the site of exposure. Draining lymph node cells demonstrated no exposure related changes in CD23 expression, however, a significant increase in the percent of CD40 + cells was observed in mice exposed to NRL proteins alone or concurrently with glutaraldehyde. These studies suggest that the observed immunomodulation by glutaraldehyde does not result from an increase in the dermal penetration of NRL proteins, but glutaraldehyde may enhance antigen presentation and B cell activation.