AIMS/HYPOTHESIS. Enterovirus infections are among the environmental risk factors potentially contributing to the pathogenesis of Type 1 diabetes. The aim of this study was to evaluate virus-host interaction by analysing the enterovirus antibody levels in subjects carrying different HLA-DR alleles associated with either increased or decreased risk of Type 1 diabetes. METHODS. Antibodies against coxsackievirus B4 were measured to study immune responses induced by natural enterovirus infections and against poliovirus 1 to study immune responses induced by immunisation by enterovirus antigens (vaccine). Antibodies against the mumps virus were measured as a control. Study subjects included siblings of children with Type 1 diabetes taking part in the Childhood Diabetes in Finland (DiMe) Study and carrying either HLA-DR risk (DR3 and/or DR4) or protective (DR2) alleles. RESULTS. Children with either the HLA-DR3 or HLA-DR4 allele and those with both these risk alleles had higher Coxsackie B4 antibody levels than children carrying the HLA-DR2 allele ( p=0.01, p=0.01 and p=0.008, respectively). High responders (IgG levels higher than 75 percent) were also more frequent among genetically susceptible children compared to children with the protective DR2 allele (27% vs 12%) ( p