Type 1 diabetes is preceded by the appearance of islet autoantibodies. Seroconversion to islet autoantibodies is greatest around 1 yr of age and is more frequent in children born to fathers with type 1 diabetes as compared to children born to mothers with type 1 diabetes. Here we asked whether changes in beta-cell function in the neonate and infant reflect variations in the incidence of islet autoantibody seroconversion. Insulin, proinsulin, and c-peptide concentrations were measured in sequential samples taken from birth to age 2 yr in 103 children who had a first degree relative with type 1 diabetes and who had been followed for islet autoantibody seroconversion. Serum insulin and proinsulin concentrations were highest at birth declining by age 3 months and stable thereafter until age 2 yr. C-peptide concentrations, proinsulin/insulin, and proinsulin/c-peptide ratios were stable from age 3 months. No differences were observed between children who developed islet autoantibodies and children who remained islet autoantibody negative. Children born to a mother with type 1 diabetes had higher birth concentrations of insulin (p = 0.005) and proinsulin (p = 0.014) as compared with children of non-diabetic mothers. Increased insulin concentrations in children of type 1 diabetes mothers persisted until age 6 months. In conclusion, we could not relate excursions in beta-cell hormones to autoantibody development, but suggest that the higher exposure to insulin and proinsulin in neonates born to mothers with type 1 diabetes may be linked to the relative protection against islet autoantibody seroconversion observed in these children.