We summarize current understanding of the genetics of human diseases and of the major histocompatibility complex related factors regulating immune responsiveness. Special factors are involved in atopic diseases as a result of the intersection between the immune system, the targets in the tracheobronchial tree and the endocrine, neurologic and genetic mechanisms affecting both the effectors and the targets. The evidence from investigations of human subjects and their families and from laboratory animals for the underlying genetic and immunologic mechanisms of asthma are reviewed. The genetic control of asthma is complex. The evidence suggests a gene or genes associated with and linked to HLA. The disease phenotype may also be regulated by genetically determined levels of IgE and the outcome of the balance between immune response and immunosuppression.