Chickens Inoculated with herpesvirus of turkeys or with apathogenic or attenuated vaccine strains of Marek's disease virus (MDV) developed a T-cell-medlated Immune response to Marek's disease (MD) tumor cells. This Immune response was detected In a 4-hour ⁵¹Cr-release assay In which effector cells obtained from spleens of vaccinated chickens were reacted with ⁵¹Cr-labeled target cells of an MD lymphoblastold cell line (MSB- 1). The cytotoxic effector cells generated by the vaccine viruses had characteristics similar to those noted previously for anllMSB- 1 effector cells generated by MDV. The immune response was specific to MSB-1 cells, because another target cell line (TL T) antlgenically unrelated to MSB-1 cells was not lysed by the effector cells nor did the unrelated target cells inhibit the cytotoxicity of effector cells against MSB-1 target In a cold-target Inhibition assay. Because MS8-1 cells contain MD tumor-associated surface antigen, we postulated that the Immune response detected in the vaccinated chickens may be directed against this antigen and that the antitumor antigen Immunity may playa role in the mechanism of vaccine protection against lymphoma development by pathogenic MDV.