The IgG response to Epstein-Barr virus (EBV) early antigens [BHRF1 (p 17.1), the viral homologue of bcl-2, and BMRF1 (p50.10), a DNA binding protein] was measured in patients with rheumatic disease to see whether there was any association with lymphoma. Patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), rheumatic disease patients with lymphoma, patients with lymphoma who did not have a rheumatic disease and normal individuals were tested for the presence of anti-EA peptide antibodies by ELISA. Whereas antibodies to early EBV peptides were detected only in one normal individual, patients with rheumatic diseases, especially those with either SS and/or lymphoma, had a much higher frequency of antibody detection. Antibodies to BMRF1 p50.10 were found in 7-50% of patients, and to BHRF1 p17.1 in 4-27%, depending on the group studied. Patients with lymphoma lacking a rheumatic disease had a 2-fold lower frequency of anti-BHRF1 antibodies, compared to the lymphoma plus rheumatic disease group. The increased immune response to the EBV EA proteins in the rheumatic diseases probably reflects the presence of reactivated virus, and the BHRF1 protein (the viral homologue to bcl-2) could, via inhibiting apoptosis, contribute to the lymphoproliferative nature of these diseases.