The elimination of maternally acquired, diabetes-associated antibodies from the peripheral circulation of infants was studied in a population of 47 mothers and their newborn infants from families in which at least 1 first degree relative had type 1 diabetes. Blood samples were taken from the placental cord; from the infant at follow-up visits at the ages of 3, 6, 9, 12, 18, and 24 months; and from the mother at the time of delivery. The samples were analyzed for cytoplasmic islet cell antibodies (ICA), insulin antibodies (IA), autoantibodies to the 65-kDa isoform of glutamic acid decarboxylase (GADA), and autoantibodies to the protein tyrosine phosphatase-related IA-2 antigen (IA-2A). The mean elimination times for ICA, IA, GADA, and IA-2A were 3.1, 3.1, 4.5, and 4.3 months (P = NS), respectively. The initial levels of IA, GADA, and IA-2A in the cord blood correlated closely with the elimination time (r(s) = 0:84-0.91; P < 0.001). The mean proportions of ICA, IA, GADA, and IA-2A still detectable were 18%, 21%, 30%, and 20%, respectively, at 3 months; 2.2%, 14%, 10%, and 6% at 6 months; and 0.3%, 15%, 2.3%, and 5.1% at 9 months. One infant still tested positive for GADA at the age of 12 months, whereas all of the other antibodies had been eliminated by that age. When observing the natural history of beta-cell autoimmunity or when screening for secondary prevention in young children, cross-sectional autoantibody analyses do not provide sufficient information. Repeated testing is to be recommended in young children. In infancy, increasing antibody levels most likely reflect de novo synthesis of diabetes-associated autoantibodies.