We have recently reported an increase in HLA-DR1 in 52 patients with thyroid epithelial cancer from Eastern Hungary (Juhasz et al., 1986). We have now investigated the association of IgG heavy chain markers (Gm) in 50 patients with this disease and explored possible interaction between Gm and HLA in modifying the risk for thyroid cancer. No Gm phenotype showed significant increases in the patients compared to 168 local controls. When both Gm and HLA, however, were considered, a marked heterogeneity in risk was noted. The odds ratio for DR1+fb+ homozygotes was 37.5, for DR1+fb- individuals 6.0 and for DR1-fb+ individuals 2.6 (DR1-fb- = 1.0). Thus Gm and HLA interact to enhance greatly the risk of thyroid cancer.