We studied the prevalence of antiperinuclear factor (APF), an antibody frequently (50-80%) present in sera of patients with rheumatoid arthritis (RA), in different groups of patients. Sera from 123 patients with RA and 28 patients with recent Epstein-Barr virus (EBV) infection showed APF in 63 and 51% of the patients, respectively. These frequencies were significantly increased (p0.001) when compared with 123 healthy blood donors (12%) and in 58 patients with herpes virus infections other than EBV (18%). Relations with other EBV elicited antibodies in RA and the relevance of EBV in RA are discussed. Our data suggest that EBV might be the immunogen for APF, an antibody, until now considered to be an autoantibody.