Recent epidemiologic studies of the determinants and natural history of IDDM using HLA typing and detecting islet cell antibodies have shown that HLA-identical siblings of probands with IDDM are at extremely high risk of developing IDDM, and that islet cell antibodies and glucose intolerance usually appear long before clinical manifestations. Thus, the disease often has a long latent period. The epidemiologic characteristics of the disease, in particular relating to variation in age of onset and seasonal variation, must now be reinterpreted in the light of these observations. It appears that the variation in seasonal onset and the age distribution probably reflect the effects of factors that precipitate clinical manifestations of the disease rather than those that are directly responsible for initiating pancreatic beta-cell destruction. The ability to identify individuals at high risk of developing IDDM now allows investigations designed to identify factors responsible for initiating pancreatic beta-cell destruction, and many ultimately result in the application of preventive measures for the disease.