Ninety-four patients with seropositive rheumatoid arthritis (RA) were typed for HLA-A, B, C and DR antigens and for immunoglobulin G (Gm) allotypes. Isolated IgG from patient serum was used to avoid interference of IgM rheumatoid factor (RF) with Gm typing in sera with high IgM-RF titer. Besides the association of seropositive RA with the antigen DR4 and an earlier disease onset in DR3/DR4 heterozygotes, we found the uncommon Gm phenotype Gm(1,2;21) significantly more often in our patient group than in healthy controls. Combination of HLA-DR and Gm data shows that individuals with both DR4 and Gm(1,2;21) are at a particularly high disease risk.