Latex allergy remains a serious risk for health care workers with past prevalence rates reported to range from 2.7-12%. Exposure may occur through inhalation as latex proteins bind to glove powders and are aerosolized during donning and removing gloves or through dermal exposure. Although hand dermatitis has been accepted as a risk factor, little is known of the relative contribution of the two routes of exposure to the development of sensitization. Animal models (BALB/c mice and hairless guinea pigs) have been used to evaluate the role of dermal exposure in the development of latex sensitization and to compare the potential for sensitization by the two routes. In vitro penetration studies using human surgical specimens and hairless guinea pig skin have demonstrated the importance of skin condition in the penetration of latex proteins with less than 1% of the applied dose of non-ammoniated latex (NAL) penetrating intact skin while as much as 30% penetrated through abraded skin. Exposure of BALB/c mice to 25microg NAL every 5th day by the dermal or intratracheal (i.t.) routes resulted in similar levels of latex specific IgE as measured by ELISA. A robust latex specific IgA response was seen in animals exposed by the i.t. route as compared to the dermal route. Upon respiratory challenge with methacholine, non-specific airway hyper-reactivity was dose-responsively increased and positively correlated with total IgE levels in animals exposed to latex proteins by either the i.t. or dermal routes. Immunoblot analysis revealed a different spectrum of sero-recognition of individual latex protein when exposure was via the i.t. versus the dermal route. Intervention strategies have been aimed at reducing the powder and latex protein content of gloves. Although these efforts have been observed to reduce the prevalence of symptoms in sensitized individuals, these data raise concerns regarding dermal exposure resulting from the continued use of low protein latex gloves. This work was supported in part by NIEHS interagency agreement #Y1-ES-0049-03.