Heteroconjugate antibodies are generated by covalently linking two mAbs with different specificities. When anti-CD3 mAb, capable of activating effector T cells, is coupled to anti-herpes simplex virus (HSV) mAb, which binds HSV antigens on virally-infected target cells, the resulting heteroconjugate antibody can be used in vitro to enhance anti-HSV immunity. Specifically, these heteroconjugate antibodies can augment anti-HSV immunity among lymphocytes previously lacking cytotoxicity against HSV-infected target cells. However, the efficacy of these specialized reagents in enhancing anti-HSV immunity in vivo has not been determined. We report here that anti-HSV heteroconjugates used in an adoptive transfer murine model of HSV-1 infection inhibited HSV replication in vivo and improved long-term survival. These results demonstrate that heteroconjugate antibodies have a potential therapeutic role in enhancement of anti-HSV immunity.