The prevalence of autoantibodies against the 65 kD isoform of glutamic acid decarboxylase (GAD65Ab), insulin (IAA), islet cells (ICA), thyroid peroxidase (TPOAb) and thyroglobulin (TgAb), in relation to HLA-DR types, was assessed in 310 (HLA in 280) twelve-year-old children during three-year follow-up. Altogether, 26.8% (83/310) of the children were found to carry at least one autoantibody. The HLA-DR3/DR4 genotype was significantly more prevalent in the subgroup of children GAD65Ab-positive on at least one occasion than among GAD65Ab-negative children [33% (2/6) vs. 5% (12/274); p = 0.031, as was the HLA-DR4/x genotype among children seropositive for at least one thyroid autoantibody, compared to the corresponding seronegative subgroup 152% (34/65) vs. 34% (74/215); p=0.01]. The proportion of children seropositive in at least one of the three tests was 1.9% (6/310) for GAD65Ab, 2.6% (8/310) for IAA, 5.2% (16/310) for ICA, 11.3% (35/310) for TPOAb and 19.4% (60/310) for TgAb. All autoantibodies except GAD65Ab tended to disappear during follow-up, and at the three-year follow-up IAA had disappeared in 50% (2/4) of cases, ICA in 67% (6/9), TPOAb in 30% (6/20) and TgAb in 38% (18/47) of cases. The turnover of seropositive subjects and the large proportion of children seropositive for at least one islet or thyroid autoantibody during a three-year follow-up suggest transient autoantibodies to be more common than is discernible in cross-sectional investigations.