The epidemiologic study of insulin-dependent diabetes mellitus (IDDM) has provided evidence for both a genetic and an environmental component in the etiology of the disease. The characteristics of IDDM, such as incidence and prevalence, and the worldwide variations therein, have prompted research into the areas of both environmental and genetic influences. While animal studies have strongly implicated an environmental agent, such as a virus, as the initiator of the disease process, it appears that such an agent needs a genetically susceptible individual in order to be effective. A coexisting approach to the study of the environmental etiology of IDDM involves immunogenetics. Recent technological advances in the study of the human genome have prompted research particularly in the HLA region of chromosome 6, where an IDDM susceptibility gene or genes are thought to lie. The combined knowledge regarding the environmental and genetic roles and their probable interaction will be helpful in understanding the etiology of the disease, if not directly leading to a mode of prevention of the disorder.