Severe disease associated with cytomegalovirus (CMV) infection is still a major problem in patients who undergo transplantation. Support of the patients' immune defense against the virus is a major goal in transplantation medicine. We have used the murine model of CMV (MCMV) to investigate the potential of a cell-based strategy to support the humoral antiviral immune response. Immunocompetent C57BL/6 mice were infected with MCMV, and memory B cells from the immune animals were adoptively transferred into T-cell– and B-cell–deficient RAG-1^−/− mice. Following MCMV infection, a virus-specific IgG response developed within 4 to 7 days in the recipient animals. Concomitantly, a significant reduction in viral titers and DNA copies in several organs was observed. In addition, the memory B-cell transfer provided long-term protection from the lethal course of the infection that is invariably seen in immunodeficient animals. Transfer of memory B cells was also effective in protecting from an already ongoing viral infection, indicating a therapeutic potential of virus-specific memory B cells. T cells were not involved in this process. Our data provide evidence that a cell-based strategy to support the humoral immune response can be effective to combat infectious pathogens in severely immunodeficient hosts.