Cell-mediated immunity to the transmissible venereal tumor (TVT) of the dog was studied by use of a 51Cr release cytotoxicity assay. Peripheral blood lymphocytes (PBL) of dogs in which the TVT had regressed were shown to be cytotoxic to the tumor cells in contrast to PBL of normal dogs and animals during progressive tumor growth, which were not cytotoxic in addition, sera of dogs in which the TVT had regressed could be demonstrated to mediate antibody-dependent cellular cytotoxicity (ADCC) with normal dog lymphocytes or cytotoxic PBL as effector cells. With cytotoxic lymphocytes, the ADCC effect could be observed in addition to the direct cytotoxic effect.