The current concept of the pathogenesis of insulin-dependent diabetes mellitus (IDDM) is based on the view that environmental factors, either alone or in combination, trigger in a genetically, susceptible individual an autoimmune process which leads to the destruction of the insulin-secreting beta cells. The identification of environmental risk factors for IDDM is of utmost importance with regard to possibilities for implementing preventive measures. Studies on the interaction between genetic and environmental factors may be complicated by the observations that genetic markers, e.g. HLA risk alleles, may vary from one population to another, and combinations of predisposing genes may differ between populations. In addition, the role of a given environmental trigger in initiating the autoimmune process may be variable in various individuals depending on the genetic set-up and other host-related characteristics. As prevention trials are already being initiated, and genetic screening is essential in the identification of individuals at increased risk of IDDM, it is crucial to learn more about the interaction of genetic and environmental factors in this disease.