Allergy and chemical sensitivity are closely related disorders in which environmental exposures produce inflammatory reactions. For allergy, environmental proteins bind to IgE antibody on mast cells leading to the release of inflammatory mediators. In chemical sensitivity, low molecular weight chemicals bind to chemoreceptors on sensory nerve C-fibers leading to the release of inflammatory mediators. Clinical manifestations are similar in the two conditions. The overlap between the two conditions has a basis in mechanism, so the similarity of clinical manifestations and high percentage of individuals with both conditions may have a biological basis. Chronic exposures can lead to adaptation phenomena. Depression has been associated with both allergy and chemical sensitivity. Both the allergic and chemical irritant responses may be subjected to conditioning so that the response is triggered by other stimuli. Evidence for conditioning is strongest for allergy. Both allergy and chemical sensitivity can be acquired in association with irritant exposures.