Studies were conducted to investigate the role of dermal exposure to Perfluorooctanoic acid (PFOA), an immunosuppressant with widespread use as a carpet and fabric protectant, on the hypersensitivity response to ovalbumin in a murine model. BALB/c mice were exposed dermally to concentrations of PFOA ranging from 0.01-2.0% (0.25-50mg/kg) for 4 days. In hypersensitivity studies, mice were also intraperitoneally injected with 7.5 ug ovalbumin and 2mg alum on days 1 and 10 and in some studies, intratracheally challenged with 250 ug ovalbumin on days 17 and 26. Endpoints for studies included body and organ weights and cellularities, IgE, airway hyperreactivity, and lung histopathology. Following exposure to PFOA, an increase in liver weights and a decrease in thymus and spleen weights and cellularities were observed. Similar immunomodulatory trends were demonstrated in mice co-administered PFOA and ovalbumin. Greater than a 2-fold increase in total IgE was demonstrated when mice were co-exposed with concentrations of PFOA ranging from 0.75-1.5%, while the ovalbumin-specific IgE response peaked after a 3-fold increase (p<0.01) in 0.75% PFOA co-exposed animals as compared to the ovalbumin alone exposed animals. Antigen-specific airway hyperreactivity was increased (p<0.05) in the in the 1.0% PFOA co-exposed group, with a dose-responsive pleiotropic cell response characterized by eosinophilia and mucin production, in animals co-exposed to concentrations of PFOA up to 1.0%, as compared to the ovalbumin alone exposed animals. PFOA was demonstrated to be immunotoxic in a murine model following dermal exposure, with an enhancement of the hypersensitivity response to ovalbumin, suggesting that PFOA exposure may augment the IgE response to environmental allergens.