Human endogenous retroviruses (HERVs) and herpesviruses have been associated with the development of multiple sclerosis (MS). These virus groups interact with each other and have been shown to induce synergistic immune responses. Here, we focus on the possible role of herpesviruses as contributing factors in HERV activation. We demonstrate the ability of HSV-1, HHV-6, and VZV antigens to induce higher RT activity in peripheral lymphocytes from MS patients vs. controls during the first 6 days post-antigen stimulation. On subsequent days, only VZV can sustain the increase in the RT expression in cells from MS patients. The RT induction does not depend on herpes replication.