Renewed concern that smallpox virus might be employed as a bioterrorism agent has led to an early implementation of a limited vaccination program. Because eczema vaccinatum is a feared complication of the Vaccinia vaccine, stringent criteria have excluded persons who currently suffer from atopic dermatitis (AD), or who have previously suffered from AD, and even close contacts of persons who have AD, from vaccination. The above criteria are estimated to exclude at least 50% of the current US population from voluntary immunization. In the event of a bioterrorism attack, however, such exclusion criteria could not be maintained, since mass vaccination would have to be initiated immediately to prevent further spread of the virus. The goal of this proposal is to identify which clinical subgroups of AD are at risk for Vaccinia complications, based upon either immunogenetic criteria (the prevailing hypothesis), or an alternate hypothesis, based upon abnormalities in epidermal barrier function. Two pathophysiologic mechanisms have been proposed to explain the increased propensity of persons with AD to develop bacterial and viiral infections. One hypothesis postulates that AD is an external manifestation of inherited immune defects, while alternatively we suspect that it could be the skin's antimicrobial/permeability barrier that primarily account for viral dissemination in AD. This study will first determine who is at the highest risk of developing eczema vaccinatum, comparing skin barrier functional measure-ments and biochemical parameters in various putative AD clinical subgroups to determine permeability barrier status. In the same AD cohorts, we will simultaneously assess a panel of immuno-genetic markers of abnormal TH2 cell function, including alterations in IL-4, -5, -13, -18, and IFN gamma. Results of these studies will first, alllow physicians to use the one or both approaches to determine who is at the highest risk for eczema vaccinatum. Second, these studies will potentially allow physicians to pretreat patients who have AD or related disease subgroups, but still require the Vaccinia vaccine, to decrease the risk in the eczema vaccinatum. In summary, the short-term goals of this study are to determine which persons suffering from AD or a history of AD can safely receive the Vaccinia vaccine; and to determine if skin pretreatment decreases the risk of eczema vaccinatum in patients at high risk who must receive the Vacciniia vaccine. The long-term goals of this study are to determine the relative contributions of epidermal antimicrobial and permeability barrier defects vs. immunogenetic abnormalities for the development of disseminated viral infections in patients with AD.