Macrophages and T lymphocytes play an important role in recovery from viral infections. During mouse hepatitis virus (MHV-A59) infection, a clear virus-specific class II-restricted cytotoxic T-cell response is generated. Transfer of these CD4+ cytotoxic T cells (CTL) into naive mice protects against a lethal challenge with MHV. However, their in vivo antiviral effector mechanism is not yet clear. To further investigate a possible effector mechanism, we studied the effect of adoptive transfer of CD4+ CTL on virus localization in spleen and liver. We showed that adoptive transfer of virus-specific T cells does not affect localization of MHV-A59 in different macrophage subsets. Interestingly, a rapid and large infiltrate of CD4+ T cells in and around MHV-A59-infected foci in the liver was observed early in infection, whereas no CD8+ T cells were detectable. Moreover, transfer of virus-specific T cells resulted in significantly decreased viral titres in the liver and spleen and a marginally increased anti-MHV-A59 IgM production. These results imply an important role for virus-specific CD4+ CTL in elimination of infectious MHV-A59 and induction of an effective immune response in the absence of CD8+ CTL.