Currently, there are three markers that are being studied with the potential to give a high positive predictive value for the development of type I diabetes (insulin-dependent diabetes caused by autoimmune beta-cell destruction) and that can be utilized to predict the disease in susceptible relatives: 1) high-titer cytoplasmic islet cell antibodies, 2) insulin autoantibodies detected with fluid-phase radiobinding assays, and 3) first-phase insulin release after intravenous glucose less than 1st percentile. With the combination of these assays, it seems to be possible to identify first-degree relatives with a high probability of developing type I diabetes within a limited time span (i.e., less than 10 yr). The ability to predict type I diabetes with selected assays will allow trials for prevention of diabetes and trials to assess whether prediction will decrease morbidity and mortality at onset of diabetes.