Thy-1 alloantigens on murine thymus cells are weak immunogens in vivo for PFC responses in the absence of other antigenic disparities between the donor and recipient. Our previous work showed that non-H-2 alloantigens acted as helper determinants to augment anti-Thy-1 PFC responses. In this report we demonstrate that strong helper antigens are also produced by infection of donor thymus cells with viruses such as HSV-1, NDV, or vaccinia. This helper effect (as much as 30-fold) for a cellular antigen, requires linked recognition (expression of Thy-1 and virus in the same cell membrane), is T-dependent, antigen- (virus) specific, and is Thy-1-specific. The recognition of the viral helper sites is not restricted by the MHC genotype of the thymus cell donor, indicating that host reprocessing of antigen occurs. These are the first results that show that adventitious antigens may function as helper determinants for antibody responses to native membrane antigens and may be the mechanism that initiates several forms of acute post-viral autoimmune disease.