Leu-19 antigen is a 200-220 kDa surface glycoprotein, initially detected on natural killer (NK) cells exhibiting non-major histocompatibility complex-restricted cytotoxicity. Using a monoclonal antibody (mAb) directed against the Leu-19 molecule, we were unable to identify NK cells immunohistologically in cryostat sections of neuroectodermal tumors. Instead, mAb Leu-19 cross-reacted with the surfaces of the tumor cells, except for melanomas. It stained mesodermal tumor cells less intensely and did not stain those of carcinoma metastases. In three plasmacytomas, cells were observed, most likely NK cells, which extend Leu-19-positive cell processes towards to the unstained tumor cells. Furthermore, the Leu-19 antigen was identified on physiological tissues, especially on all neuroendocrine cells analyzed. The cross-reactions observed with Leu-19 mAb were confirmed using mAb NKH-1, which is also directed against the Leu-19 molecule. Thus, the expression of Leu-19 on neuroectodermal cells is another example of antigen sharing between specialized immune cells and the nervous system.