Cooperation between oncolytic herpes simplex virus (HSV) and host effector immune mechanisms has been previously described. In the present study, we investigated the mechanism underlying such cooperation in a murine syngeneic model of ovarian carcinoma. Therapeutic administration of HSV-1716, a replication-restricted mutant, resulted in significant reduction of tumor growth and a significant survival advantage. Intratumoral injection of HSV-1716 induced expression of IFN-gamma, MIG, and IP-10 in the tumor. This was accompanied by a significant increase in the number of tumor-associated NK and CD8+ T cells expressing CXCR3 and CD25. Ascites from HSV-1716-treated animals efficiently induced in vitro migration of NK and CD8+ T cells, which was dependent on the presence of MIG and IP-10. Murine monocytes and dendritic cells (DCs) were responsible for the production of MIG and IP-10 upon HSV-1716 infection. In monocytes, this was partially abrogated by neutralizing antibodies against IFN-alpha and -beta, thus indicating a role for type-1 IFNs in the reported effect. Human ovarian carcinomas showed high numbers of monocytes and DCs. Upon HSV-1716 infection, human monocyte-derived DCs produced large amounts of IFN-gamma and upregulated MIG and IP-10 expression. These results indicate that HSV-1716 induces an inflammatory response that may facilitate antitumor immune response upon oncolytic therapy.