Human cell lines of hematopoietic origin were tested for production of tumor necrosis factor (TNF) hTNF activity was not found in supernatants of cell lines of T-cell, monocytic, or promyelocytic origin. Partially purified hTNF has a molecular weight of approximately 70,000, has no interferon activity, is acid labile, is destroyed by heating at 70°C for 1 hr, induces cross-resistance to mouse TNF in vitro, and causes hemorrhagic necrosis of Meth A mouse sarcoma in the standard in vivo mouse TNF assay. Tests with a panel of 23 human cancer cell lines showed that hTNF is cytotoxic for 7 cell lines, cytostatic for 5, and has no effect on 11. Comparative studies with human a, fi, and y interferons indicated that sensitivity to hTNF and interferon can be distinguished. Combined treatment with hTNF and a or y interferon resulted in a synergistic cytotoxic effect.