Murine cytomegalovirus (MCMV) inhibits antigen-specific cytotoxic T lymphocyte (CTL) priming in vivo (Campbell et al., 1989). To address the mechanism of this immune suppression, two possibilities were considered: (1) MCMV directly interferes with in vivo priming of CTL precursors (CTLp), or (2) MCMV suppresses T helper cell functions necessary for CTL priming. We therefore quantitated T helper cell function in MCMV-infected, SV40-immune mice and assessed dependency of SV40-specific CTLp priming on T helper cell activity. MCMV infection of H-2b mice significantly suppressed the frequency of IL-2 producing T helper cells generated in SV40-immune mice. This suppression was not due to alterations in the number or percentage of CD4 lymphocytes. The helper cell deficiency correlated with suppressed SV40-specific CTL activity. However, CTLp priming in vivo was found to be independent of CD4 T helper cells and IL-2. Therefore, the suppressive effects of MCMV on helper and cytotoxic T cell functions are independent, implying that MCMV directly inhibits an event in lymphocyte priming common to both helper and cytotoxic T cells.