Viral cofactors may be important in the pathogenesis of HIV infection and the development of AIDS, but their role is still imperfectly understood. Sequential serological studies were performed in a cohort of 100 homosexual men and 70 matched healthy controls over a mean period of 4 years. Of the patients, 18 were found to be HIV+ on admission to the study and 15 seroconverted to HIV+ during the follow up (seroconversion group). Serum antibodies of both IgG and IgA isotypes against Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were determined. IgG antibodies indicate past infection, while a marked increase in IgG titre or a positive IgA titre were taken to indicate active infection or reactivated latent infection. EBV and CMV infections were about two to four times more prevalent in the homosexual men both HIV– and HIV+, compared with controls. Active infections were increased in the homosexual men and particularly in the HIV+ patients. The seroconversion group revealed activation of both EBV and CMV following HIV infection. When the antibody profile of seroconverting patients at the time preceding seroconversion was compared with a matched group of 39 homosexual men who remained HIV–, no change was found in CMV antibodies, but four out of 15 (26.6%) of the patients had high titres of anti-EBV IgA preceding seroconversion, as compared with only one out of 39 (2.6%) of HIV– homosexual men (/<0.05). This suggests a role for EBV reactivation in the pathogenesis of HIV infection in some patients.