To examine the hypothesis that a hereditary factor linked to the immunoglobulin kappa constant segment (C kappa) contributes to risk of rheumatoid arthritis (RA), white persons with RA were examined for Sac I restriction site polymorphisms. RA patients were more likely to have the 5/5-kb C kappa genotype than white control subjects (relative risk 2.8, P less than 0.02). A subgroup of RA patients who were positive for serum rheumatoid factor had a relative risk of 2.4 (P less than 0.05). The subgroup without serum rheumatoid factor had an even higher relative risk of 9.7 (P less than 0.05). The results suggest that immunoglobulin kappa is an important component in the genetic predisposition toward RA.