We sought to study the prevalence of autoantibodies to various islet cell antigens in the background population of two neighboring countries with a sixfold difference in the incidence of type 1 diabetes. Serum samples were obtained from 3,652 nondiabetic schoolchildren in Finland and from 1,988 schoolchildren in the adjacent Karelian Republic of Russia. The Karelian children were divided into three groups (Finns/Karelians, Russians, and others) based on the ethnic background of their mother. The samples were analyzed for islet cell antibodies (ICAs), insulin autoantibodies (IAAs), GAD antibodies (GADAs), and the tyrosine phosphatase-like insulinoma antigen 2 (IA-2A) protein and HLA class II genotypes. The frequency of ICAs, IAAs, and GADAs did not differ significantly between the Karelian (3.5, 0.6, and 0.9%, respectively) and Finnish children (2.8, 0.9, and 0.5%, respectively). Similarly, the frequency of multiple (> or = 2) autoantibodies was similar in both countries (0.5 vs. 0.6%). The frequency of IA-2A was, however, four times higher in Finland (0.6 vs. 0.15% in Russian Karelia; P = 0.03). There were no significant differences in autoantibody prevalence among the three ethnic groups in Russian Karelia. There was a falling frequency of GADAs and of positivity for multiple autoantibodies along with decreasing HLA-conferred disease susceptibility among the Finnish schoolchildren. These data indicate that beta-cell autoimmunity among schoolchildren is as frequent in Russian Karelia as in Finland, although the incidence of clinical type 1 diabetes is six times higher in Finland. However, in contrast to this general trend, IA-2As were more common in Finland. Since IA-2As usually appear late in the preclinical process, this suggests that progressive beta-cell autoimmunity is more rare in Russian Karelia.