The tumor directed cell mediated response in patients with neuroblastoma was studied in vitro by the 51Cr release cytotoxicity assay. The following results were obtained. In peripheral blood lymphocytes of disease-free and postoperative neuroblastoma patients, cytotoxic T lymphocytes (CTL) were induced in vitro against allogeneic human neuroblastoma cell (NB GOTO). Their % specific 51Cr releases were from 15.2 +/- 0.1 to 35.8 +/- 0.6&, and in some of them, specific cytotoxic activity for C-1300 murine neuroblastoma were shown (12.0 +/- 1.1%). But, nobody could be detected from patients of neuroblastoma who were preoperative or receiving chemo-radiotherapy, and as well in the control patients and other patients who had malignant tumors. Surprisingly, in Stage IV-S neuroblastoma patient, a high level of CTL appeared every time, even in the preoperative period (33.0 +/- 0.2%). The conclusion is that a clear cross activity exists in T cells mediated cytotoxic reaction between the mouse and human neuroblastoma without recognizing both major histocompatibility (MHC) determinants. Neuroblastoma cells carry specific antigenic determinants shared with both mouse and human species, that is, neuroblastoma-specific antigens have common antigenic moieties in different animal species.