The immune response against two herpesviruses has been determined in sera and matched synovial fluids of patients with rheumatoid arthritis (RA) and compared with that of a healthy control population. The increased level of antibody to Epstein-Barr virus (EBV) induced antigens in patients with RA resembles the antibody pattern observed against cytomegalovirus (CMV) induced antigens, which suggests the presence of a pathological condition in patients with RA that can reactivate latent viral infections. The antibody response against EBV and CMV observed in synovial fluids excludes the local production of specific antibodies against EBV and CMV antigens.