It has been recognized that there are considerable variations in their skin reactivity to environmental allergens as well as in immunoreactivities, even in AD patients with similar signs and symptoms. Some AD patients have high serum IgE antibody levels, while others show low levels. There are also differences in the kinds of triggering factors that are related to the development and maintenance of AD, e.g., allergic or non-allergic. Even among AD patients with high titers of serum IgE antibodies, the kinds and number of allergens involved in the exacerbation of AD are different and can change with time. The types of the underlying allergic reactions vary as well, i.e., some show immediate reactions, while others show delayed type hypersensitivity responses to environmental allergens. Thus, even AD patients diagnosed by the established criteria may have remarkably different backgrounds. When we looked over our published data, we noticed that there were differences in levels of IgE RAST and skin reactions between AD with atopic respiratory diseases (ARD) and pure AD without ARD. Levels of IgE RAST against airborne allergens, which come into the body mainly through the respiratory tract, were higher in AD with ARD, while those against allergens such as Candida albicans and Malassezia furfur, which can colonize on the skin, were higher in pure AD. In addition to these Th2-mediated immunological abnormalities, Th1-mediated DTH reaction and lymphocyte proliferation indices against airborne allergens were remarkably low in AD with ARD, whereas those against Candida albicans and Malassezia furfur were relatively preserved, although they were lower than those found in normal subjects. We understand from these findings that routes of allergen entry are important for the outcome of the resultant allergic reactions. This point of view is important answering questions such as how AD develops and how it can be prevented from the insults of each allergen.