The effect of Sindbis virus-sensitized lymphocytes on acutely infected mouse embryo fibroblasts has been studied in vitro. Sindbis virus-immune lymphocytes are capable of lysing the infected target cells bearing surface viral antigen before viral-induced lysis occurs. The cytotoxicity was virus-specific since lymphocytes sensitized to yellow fever virus were unable to kill the Sindbis virus-infected target cells. The effector cell in this in vitro assay has been shown to be a T cell, and the cytotoxic reaction can be blocked by Sindbis virus-immune serum. In distribution to lysis of infected cells by T cells, viral clearance is dependent on a population of noncytotoxic, adherent cells, probably macrophages. Further, macrophage function in this assay was virus-specific, since adherent cells from animals immunized to a second virus were unable to reduce significantly virus content. Consequently, the full expression of recovery mechanisms in this model of an acute viral infection most likely depends on a balance between lymphocyte-mediated lysis of infected cells and viral clearance by macrophages and antibody.