Segregation of chromosome #6 markers has been studied in a large family, identified by a proband with seronegative, juvenile-onset rheumatoid arthritis, which contains four other individuals with adult-onset rheumatoid arthritis (RA). Two of the adult-onset patients have classical seropositive RA. Sera from two healthy members of this family also contain rheumatoid factors (RF). Six family members had crossovers in the short arm of chromosome #6. Three individuals with recombinants between HLA-B and HLA-D were identified; three others had identifiable crossovers between HLA-D and GLO (Glyoxylase 1). Linkage analysis suggested that susceptibility to RA in this family was influenced by a dominant gene located centromeric to HLA-B. The highest lod score (1.64) was obtained for linkage to GLO at a recombination rate of zero. Inheritance of specific chromosome #6 or Gm immunoglobulin allotype markers did not appear to influence serum RF. These results agree with previous family studies which suggest that acquisition of childhood- and adult-onset RA is influenced by a common disease susceptibility gene, linked to the major histocompatibility gene complex.