Epstein–Barr virus has been associated with lupus through serologic, molecular, and experimental studies. However, the results are conficting. Our objective was to determine whether there is an association between Epstein-Barr virus and lupus. Serum samples from 100 patients with lupus were analyzed for the presence of IgG antibody against EBV-viral-capsid antigen, EBNA-1, cytomegalovirus, and herpes simplex-1. Sera from healthy blood donors served as controls. Serum levels of total IgG in 29 lupus patients and 29 controls also were evaluated. Of 87 lupus patients, 79 (90%) were positive to-EBNA-1, compared with 3 out of 45 (6.6%) from the controls (p<0.05, OR 160), while 98 (98%) were positive to viral capsid antigen, compared with 223/274 (81%) from the controls (p<0.05). No significant difference was found in the frequency of antibodies against cytomegalovirus and herpes simplex-1 in patients and controls (p>0.05). Serum levels of IgG in 29 lupus patients and 29 control subjects were similar (p>0.05). These results show an association between past Epstein-Barr virus infection and lupus, but it does not prove a viral cause. The high frequency of antibodies to EBNA-1 and viral capsid antigen could not be explained by hypergammaglobulinemia.