A series of 43 dogs with spontaneous melanomas, sarcomas, or mammary carcinomas were tested for peripheral blood lymphocytotoxicity against a range of allogeneic tumor cells in vitro on one or more occasions during therapy. All tumor-bearer groups contained a proportion of dogs showing a significant 51Cr release with increasing effector-to-target cell ratios. However, cytotoxicity was not restricted for target cells of the same histologic type as that of the effector cell donor. Some unrelated target cells more sensitive to nonspecific effects showed a greater cytotoxicity in some instances. Control effector cells from healthy dogs were nonspecifically cytotoxic for a range of tumor target cells in a similar proportion of instances. Short-term cultures of autochthonous tumor target cells were resistant to lysis in the 51Cr release assay. The findings did not provide evidence for the existence of specific tumor antigens operative to allogeneic 51Cr release cytotoxicity assays.