Using a somatic cell hybridization technique, four murine monoclonal antibodies (three immunoglobulin M and one immunoglobulin G3) were produced against a human neuroblastoma cell surface glycolipid antigen. They reacted strongly with all human neuroblastoma tumor-containing specimens and six of eight human neuroblastoma cell lines. More than 98% of each neuroblastoma cell population possessed this surface antigen, and in the presence of complement, 100% of them were killed. While melanoma and osteogenic sarcoma carried this antigen, leukemia and most Ewing's and Wilms' tumors did not. There was no cross-reaction with 30 normal or remission bone marrow samples and none with normal human tissues other than neurons in vitro. This antigen was neuraminidase sensitive, separable on thin-layer chromatogram, and did not modulate after combining with the monoclonal antibodies. These antibodies could detect less than 0.1% tumor cells deliberately seeded in the bone marrow samples. Because of their unique properties, these monoclonal antibodies may have diagnostic and therapeutic potentials.