In vivo and in vitro immunologic cross reactivity between SV40 virus transformed prostatic tissue and fetal antigens of LVG/LAK strain hamsters has been studied. The hamsters immunized with fetal antigens demonstrated significant resistance to tumor growth. Complement-dependent humoral cytotoxicity of target SV40 tumor cells in microtest plates was used to demonstrate the presence of significant antibody titer in fetal-immunized hamsters. When the immune sera were absorbed with SV40 transformed prostatic tissue, cytotoxicity indices were markedly lower than with the unabsorbed immune sera. The transformed prostatic tissue was found to have an elevated tartrate inhibited acid phosphatase indicative of the presence of epithelial components in the transformed tissue. These experiments demonstrate in vivo and in vitro cross reactviity between fetal antigens and tumor associated antigens of transformed prostatic tissue. This study suggests a similarity between fetal antigens and antigens of a specific organ tissue (prostate) transformed by a DNA oncogenic virus.