Antibiotic C1027, a macromolecular peptide with highly potent cytotoxicity to cultured cancer cells, was conjugated to monoclonal antibody 3A5 and its Fab fragment separately using SPDP as the linker agent. McAb 3A5, identified as IgG1, was directed against human hepatoma BEL-7402 cells. By ELISA, McAb 3A5 and the Fab fragment were strongly reactive with hepatoma cells and weakly reactive with KB cells. Determined by clonogenic assay against hepatoma BEL-7402 cells, the IC50 values for McAb-C1027, Fab-C1027 and C1027 were 4.2 x 10(-14), 8.6 x 10(-16) and 6.5 x 10(-16) mol.L-1, respectively. Fab-C1027 was 49-fold more potent than McAb-C1027 in cytotoxicity. Moreover, Fab-C1027 was 160-fold more potent in cytotoxicity to hepatoma cells than to KB cells, indicating selective cytotoxicity of Fab-C1027 conjugate to the target cells. Therapeutic effect of the conjugate was evaluated with hepatoma BEL-7402 xenograft in nude mice. After subcutaneous transplantation of the tumor, treatment started on day 3, iv, with equivalent dose of C1027, 0.1 mg.kg-1 x 6. Fab-C1027 and free C1027 inhibited tumor growth by 85% and 59%, respectively. Fab-C1027 conjugate showed more marked antitumor effect in vivo than free C1027.