Atopy arises from a complex interplay between immunogenetic controls and complex environmental allergens. Family studies of atopic patients indicate a polygenic control of IgE production overlayed with exposure to certain ubiquitous environmental antigens. Ultrapurified antigen studies in families indicate that HLA-D immune response genes, notably HLA-DR/Dw2, are implicated in some atopic responses. IgE-binding factors and gene regulation of proteins controlling glycosylation of them also influence the serum levels of IgE, as do the levels of at least two cytokines, IL-4 and gamma interferon.