Immunoglobulin G antibody titers to human herpesvirus 6 (HHV-6), measles virus, and cytomegalovirus (CMV) were examined in serum samples from 31 patients with Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM). Sera were drawn sequentially from the same patients less than or equal to 7 days until 3 years after onset of IM. In seropositive patients, there was a significant decrease with time after IM of the immunoglobulin G titers to the three viruses in the majority of patients; HHV-6 IgG titers decreased in 80%, measles virus IgG titers decreased in 75%, and CMV IgG titers decreased in 67%. Four patients contracted CMV infection during the observation period after IM. In these, HHV-6 IgG titers increased, while EBV and measles virus IgG titers remained essentially stationary. Polyclonal B-cell stimulation during IM is suggested to augment antiviral titers in general, but the increases of HHV-6 IgG titers during EBV and CMV infections may also be due to selective stimulation of memory B cells by related antigens or to reactivation of HHV-6 during infection with these herpesviruses.