Peripheral blood mononuclear cells (PBMC) from patients with epithelial adenocarcinoma of the ovary treated in vivo with tumor vaccines administered as viral oncolysates (VO) exhibited significant proliferative responses in vitro to VO as well as to cellular oncolysates (CO). These responses were dependent on the concentration of VO or CO. VO consisted of lysates from the same ovarian tumor cell lines 2774 and CaOV3 infected in vitro with the avirulent strain of influenza virus A/PR8/34. CO were lysates from the same ovarian tumor cell lines without virus. Depletion experiments with the OKT3 monoclonal antibody plus complement demonstrated that these proliferative responses are T cell specific and under the control of the HLA-D region. Furthermore, these T cell responses are directed against both tumor tumor cellular components and tumor HLA class I molecules. These responses can be detected as early as two weeks after the first intraperitoneal injection of VO and reach a maximum 12-16 weeks after the first application of VO for treatment. PBMC from ovarian patients that received in vivo VO exhibited insignificant proliferative responses to CO prepared from human fibroblasts or tumor cell lines of hematopoietic origin. In contrast, they exhibited significant proliferative responses to CO prepared from a human cervix tumor cell line. These results demonstrate systemic T cell activation by antigens in the tumor vaccines in patients with epithelial ovarian carcinoma after in vivo intraperitoneal administration of VO.