This chapter reviews clinical and laboratory analyses that aid in the diagnosis and management of human allergic (IgE-dependent) diseases. The diagnostic algorithm for immediate-type hypersensitivity begins with a thorough clinical history and physical examination. Once signs and symptoms compatible with an allergic disorder have been identified, a skin test and/or blood test for allergen-specific IgE antibodies may serve as primary confirmation to strengthen the diagnosis. Puncture and intradermal skin testing provide a biologically relevant immediate-type hypersensitivity response in the skin, with resultant wheal and flare reactions within 15 minutes of allergen application. Bleeding, dermatographism, and antihistamines may confound the quality of the skin test. Allergen-specific IgE antibody may also be detected in the blood using a radioallergosorbent test (RAST). Nonisotopic "second-generation" RAST-type assays have evolved to provide more quantitative, sensitive, precise IgE antibody results. In vivo provocation tests may serve as secondary confirmatory tests when the clinical history is discordant with a primary IgE antibody test result. The multiallergen screen is a qualitative RAST-type assay that detects specific IgE antibody to approximately 15 allergens that evoke a large majority of aeroallergen or food-related allergic disorders. Other useful serological assays performed in the diagnostic allergy laboratory include total serum IgE, Hymenoptera venom-specific IgG antibody, IgG precipitins for organic dusts, mast cell tryptases, and the venom RAST inhibition test. Above all, in vivo or laboratory confirmatory test results that are inconsistent with the clinical history should be repeated as for any laboratory assessment.