AIM: Reactive oxygen intermediates have been implicated in mediating the destruction of insulin-producing beta cells and antioxidant nutrients thought to protect against such a process. This study aimed to assess the associations between serum α- and β-carotene concentrations, and the risk of advanced beta-cell autoimmunity, in children with HLA-conferred susceptibility to type 1 diabetes. METHODS: This case-control study, comprising 108 case children with advanced beta-cell autoimmunity and 216 matched control children, was nested within the nutrition study of the Type 1 Diabetes Prediction and Prevention (DIPP) birth cohort. Serum α- and β-carotene samples were collected each year from the age of 1 to 6 years. For each case-control group, serum samples were analyzed up to the time of seroconversion in the case children. Associations were studied using a conditional logistic-regression model. RESULTS: Neither serum α- nor β-carotene concentration was significantly associated with the risk of advanced beta-cell autoimmunity. There was marginal evidence (P=0.049) of an inverse association between serum β-carotene concentration and the risk of developing advanced beta-cell autoimmunity at a time closest to seroconversion after adjusting for parental education, maternal age, duration of gestation, diabetes in first-degree relatives, number of earlier deliveries and maternal smoking during pregnancy. CONCLUSION: The present study data provided no clear evidence to support an association between serum α- or β-carotene concentration and advanced beta-cell autoimmunity.