Objective :To develop an agent that is more active against receptor-bearing target cells without increasing the toxic effect on non-target cells. Methods :By the use of molecular biology techniques,we designed and constructed a fusion protein 5＇IL6-TNF△ by connecting the human interleukin-6 (hIL-6) gene and a human tumor necrosis factor α derivative (TNF△) gene througha synthetic linker sequence followed by subsequent expression in E. Coli. Results: In cytotoxicity assay with myeloma cell line U266, the normal type of 5＇ IL6-TNF△ showed an antitumor activity 3 times higher than that of TNF△;and the antitumor activity of 5＇IL6-TNF△ blocked by IL-6Rwas only 1/30 of that of normal type of 5＇ IL6-TNF△. Meanwhile,the 5＇IL6-TNF△ blocked by an ti-TNF antibody did not show any cytotoxicity to U266 cells. In activity assay with L929 cells ,the toxic effect of the fusion protein was found 1/22 of that of TNF△. Conclusion: The 5＇IL6-TNF△fusion protein might be a useful cytotoxic agent in cancer treatment.