Allergy to natural latex rubber has recently been appreciated as a major cause of occupational asthma and dermatitis and intra-operative anaphylaxis. The diagnosis and epidemiology of immediate-type hypersensitivity reactions to natural rubber latex have been limited by an absence of standardized diagnostic reagents for in vivo (skin test) and in vitro (serum IgB antibody) assays. This project proposes to document the in vivo and in vitro diagnostic efficacy of three prototype latex extracts and to apply them to the study of the natural history of latex allergy. Specific Aim l involves in vitro documentation of the composition, potency, stability and inter-lot/source variation of three potential latex allergen sources: non-ammoniated and ammoniated forms o latex sap and extracts of latex gloves. In Specific Aim 2, Phase I (safety-specificity) and Phase II (sensitivity-potency) clinical studies will be conducted using protocols approved by the FDA under IND BB 4920. Fifty non-atopic or atopic but non-latex allergic individuals will be skin tested using a titration scheme where initial prick/puncture skin tests will determine the concentration range of extract to be used in subsequent intradermal skin tests. Once optimal concentrations are identified 100 latex allergic adult subjects with local (contact urticaria) to severe systemic (asthma, cardiovascular) allergic reactions to latex rubber gloves will be evaluated by skin test and serological assays. Sera from these subjects will also be analyzed in in vitro immunoassays for IgE and IgG latex antibodies using the same source latex allergens as reagents. Basophil- histamine release will be used as a referee method to clarify mismatches between diagnostic in vivo and in vitro assay results. Specific Aim 3 is to develop a safe latex glove provocation test to examine the safety of low-allergen, powder-free gloves and to evaluate subjects with mismatched skin and serological test results. Finally, Specific Aim 4 is to use the optimized diagnostic methods in epidemiological studies to document the natural history of latex sensitization and its response to avoidance measures. The long-range objective of this project is to develop standardized diagnostic reagents for latex allergy for use by practitioners and research scientists, and to define with these reagents the natural history of latex sensitivity.