In an attempt to understand the role of the different IgG subclasses in allergic disease, we have studied the subclass of IgG antibody to dust mite (HDM) and grass pollen (GP) produced as a result of natural exposure. Studies were carried out on 40 atopic children and 100 atopic adults who had never received immunotherapy. Thirty-two non-atopic adult controls were also studied. The specificity of the assay for IgG antibodies to dust mite was confirmed by inhibition with the homologous extract but not mite culture medium or fetal calf serum. IgG1 antibodies to HDM could be detected in most atopics (94%) and non-atopics (97%), and similar results were obtained for GP (81% and 100%, respectively). IgG4 antibodies to HDM were detected in more atopics (66%) than non-atopics (53%) and the difference was more marked for GP (72% vs. 19%). While the levels of IgG1 antibodies were not significantly different in the two groups, the levels of IgG4 antibodies were much lower in the non-atopics (P less than 0.001, Mann-Whitney U-test). These data show that all subjects were capable of recognizing and mounting an IgG1 antibody response to these inhaled antigens. Atopic individuals differed from normal subjects in the frequency with which they made IgG4 antibodies in response to natural exposure to both dust mites and pollen.