Antibodies against islet cell antigens are used as predictive markers of type 1 diabetes, but it is unknown whether they reflect an ongoing autoimmune process in islet tissue. We investigated whether organs from adult donors that are positive for autoantibodies (aAbs) against islet cell antigens exhibit insulitis and/or a reduced beta-cell mass. Serum from 1,507 organ donors (age 25-60 years) was analyzed for islet cell antibodies (ICAs), glutamate decarboxylase aAbs (GADAs), insulinoma-associated protein 2 aAbs (IA-2As), and insulin aAbs. Tissue from the 62 aAb+ donors (4.1%) and from matched controls was examined for the presence of insulitis and for the relative area of insulin+ cells. Insulitis was detected in two cases; it was found in 3 and 9% of the islets and consisted of CD3+/CD8+ T-cells and CD68+ macrophages; in one case, it was associated with insulin+ cells that expressed the proliferation marker Ki67. Both subjects belonged to the subgroup of three donors with positivity for ICA, GADA, and IA-2-Ab and for the susceptible HLA-DQ genotype. Comparison of relative beta-cell area in aAb+ and aAb- donors did not show a significant difference. Insulitis was found in two of the three cases that presented at least three aAbs but in none of the other 59 antibody+ subjects or 62 matched controls. It was only detected in <10% of the islets, some of which presented signs of beta-cell proliferation. No decrease in beta-cell mass was detected in cases with insulitis or in the group of antibody+ subjects.