To further investigate the possibility of a cause and effect relationship between exposure to house-dust mite (HDM) allergens and respiratory disease associated with dust mite sensitivity, we compared schoolchildren living in the Alps, where exposure to HDM is low, with those living at sea level, where it is high. The study included 933 schoolchildren from the fourth and fifth grades. The protocol included the standardized 1978 American Thoracic Society (ATS) questionnaire for children, skin testing using common aero-allergens and controls, and antigenic measurements of dust samples from mattresses (Group I antigen). The prevalence of asthma with positive skin test to HDM and the overall prevalence of positive skin test to HDM were significantly lower in mountain schoolchildren. The mean geometric HDM antigenic level in mattresses was much lower in the Alps (0.36 micrograms/g dust) than at sea level (15.8 micrograms/g dust). In contrast, the prevalence of hay fever and positive skin test to grass pollens as well as the overall prevalence of positive skin tests to grass pollens were significantly higher in the Alps. These data illustrate a striking relationship between exposure to environmental allergens and atopic sensitization.