Relatives of patients with insulin-dependent diabetes mellitus (IDDM) carry an increased risk of developing IDDM. A number of studies that focus on the development of IDDM in such relatives, and the metabolic, immunologic, and viral factors involved are reviewed. These studies indicate that the destructive process in the beta-cells goes on for varying and often extended periods before the development of clinical disease. Thus, the events surrounding the time of clinical diagnosis may be of importance only as triggering mechanisms. Future studies may, therefore, be better directed toward long-term surveillance of the metabolic, viral, and immunologic status of first-degree relatives of IDDM subjects and the associations of these factors with genetic influences such as HLA-DR types or subtypes.