Thy-1 alloantigens on murine thymus cells are weak immunogens in vivo for plaque-forming cell (PFC) responses in the absence of other antigenic disparities between the donor and recipient. Non-H-2 alloantigens were previously shown to act as helper determinants to augment anti-Thy-1 PFC responses. This report demonstrates that strong helper antigens are also produced by infection of donor thymus cells with viruses such as herpes simplex virus type 1, Newcastle disease virus 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 Thy-1-specific. The recognition of the viral helper sites is not restricted by the major histocompatibility complex genotype of the thymus cell donor, indicating that host reprocessing of antigen occurs. Thus, 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.