The recent dramatic rise from 0.1 to 7.3% in the prevalence of adult asthma in the South Fore area of the Eastern Highlands of Papua New Guinea (PNG) has not been matched by a similar increase in asthma in the adjacent Asaro valley, where the prevalence remains extremely low at 0.3%. While the living conditions of these two populations appear comparable, the mean density of house dust mite (principally Dermatophagoides pteronyssinus) in blankets of residents in the Asaro valley was found to be significantly lower (283/g dust) than that of a corresponding random selection in the South Fore (1371/g dust). Since from 200 to 600 mites per g dust have been reported to constitute a risk factor for asthma, the data suggest that the relative risk for asthma in the Asaro valley population is low compared with that in the South Fore. In randomly selected sera, both IgE and IgG antibodies to D. pteronyssinus from the Asaro valley were comparable with those of a group of non-asthmatics from the South Fore (mean 4.39 vs 3.43 U/ml for IgE antibodies and 1832 vs 1815 U/ml for IgG antibodies for Asaro valley vs South Fore, respectively) but significantly lower (P < 0.001) than corresponding data for subjects in the South Fore with asthma (108.6 U/ml and 3365 U/ml, respectively). This study emphasizes the interplay between genetic and environmental factors in determining the development of asthma, and highlights the importance of house dust mites in the pathogenesis of asthma in the Eastern Highlands of Papua New Guinea.