Abstract: Bleomycin A6 (A6),a single component of bleomycin complex, is highly active against human liver cancer cells in vitro and xenografts in nude mice. A6 was conjugated to monoclonal antibody Hill directed against human hepatoma BEL-7402 cells, using Dextran T40 as an intermediate. The conjugate consisted of a coupling molar ratio of 1 : 264 for Hlll and A6, and retained 6.3% of A6 activity. As determined by clonogenic assay with hepatoma BEL-7402 cells exposed to the agents for 1 h, the IC₉₀ values for Hlll-A6 conjugate, free A6 and M3- A6 conjugate (an irrelevant conjugate) were 0.17μ mol/L , 17μ mol/L and 7 μ mol/L respectively. The cytotoxicity of Hill-A6conjugate to target cells was markedly blocked by unconujgated Hill but not by irrelevant monoclonal antibody M3. The Hlll- A6 conjugate exhibited 78% inhibition on the growth of hepatoma BEL-7402 xenografts in nude mice, whereas the equivalent doses of free A6, M3 -A6 conjugate and Hlll plus A6 mixture showed approximately 30% inhibition. Histopathological examination showed no toxic changes in the liver, lung, kidney and bone marrow in the Hlll-A6 conjugate- treated animals. These results suggest that the conjugate of monoclonal antibody and bleomycin A6 exhibits specific cytotoxicity to target liver cancer cells and the conjugate is highly effective against liver cancer xenografts in nude mice with more marked tumor inhibition than free A6 at comparable dose levels.