Background: Although some studies have shown genetic control of specific IgE responses to purified grass allergens, studies with other allergens have not supported this. The extent of such control for house dust mite (HDM) (Dermatophagoides pteronyssinus) allergens is unclear. Objective: We sought to determine the extent to which genetic factors control the specificity of IgE responses to individual HDM allergens by comparing the immunoblot patterns of IgE binding of serum from monozygotic and dizygotic members of a large cohort of Australian twins. Methods: HDM proteins separated by sodium dodecylsulfatepolyacrylamide gel electrophoresis were immunoblotted with sera from 317 twin pairs in which at least one twin had at least a weak HDM skin test response. Concordance levels for IgE binding to the individual HDM components were compared in the subset of 142 pairs of twins in which both twins were allergic to HDMs (skin prick test wheat diameter, > 3 mm). Results: Over all 36 blotted bands, the mean case-wise concordance was 41% for monozygotic twins and 17% for dizygotic twins. Of the components detected, only those of molecular weights 23 kd and 16 kd were significantly different between the groups (p < 0.01). Differences observed between the monozygotic and dizygotic twins could be partly explained by overall IgE hyperresponsiveness. Conclusion: Evidence for genetic control of IgE responses to 36 IgE-binding HDM components from a large sample of twins showed significant differences in concordance for two components and nonsignificant differences for several others. In the monozygotic twins, concordance never exceeded 67% for any band, and most monozygotic individuals recognized components their co-twin did not. Genetic control of overall atopy in monozygotic twins is far stronger than that controlling specific sensitization to HDM allergens.