Islet cell antibodies (ICA), insulin autoantibodies (IAA) and islet cell surface antibodies (ICSA) together with C-peptide were determined in 1031 healthy schoolchildren to evaluate the frequency of autoimmune reactions towards endocrine pancreas and its relation to insulin secretion in non-diabetic children. The prevalence of ICA (levels > 6 JDF units) was 1.4% (14/1012) while 44 children (4.3%) were ICSA-positive and 40 (4%) had IAA. Girls had higher titres of ICSA than boys. Young children (7-8 years) more often had IAA than 12-13-year-old children who, however, had ICA three times more often than the young children. There were no clear associations between the different antibodies. Of the children, 2.4% had very low post-prandial serum C-peptide values (< or = 0.25 nmol/l). Serum C-peptide was higher in girls than in boys (P < 0.001) and in older children than in younger (P < 0.001). Girls with low levels of ICA had high C-peptide values, while girls with high ICA titers had low C-peptide values, the latter perhaps indicating partial beta cell loss. IAA and ICSA were not related to C-peptide values but both positive ICSA and high C-peptide values were most common in the autumn (P < 0.02 and P < 0.0001, respectively). One of the ICA-positive children developed diabetes in 1991, 4 years after the blood sample was taken. Since after 5 years only one of the children has developed IDDM, it can be concluded autoimmune reactions towards endocrine pancreas and insulin may occur in many children without the development of manifest diabetes. Those with high ICA titers may have lost so many beta cells that their insulin secretion is affected, which in some cases might lead to diabetes many years later.