Type 1 diabetes mellitus (T1D) is an immune-mediated disease in which insulin-producing ß-cells are destroyed, resulting in life-long dependence on exogenous insulin. It is a chronic, potentially-disabling disease that represents a major public health and clinical concern. The incidence of T1D is increasing each year and is approaching an epidemic level in some countries. Unfortunately, the increase in T1D is greatest in children under the age of five years. The goals of the TrialNet Natural History Study of the Development of T1D are therefore to gain information about the pathogenesis and natural history of T1D, and to facilitate the assessment and recruitment of individuals who might qualify for T1D prevention trials.