In this study, we attempted to develop tumor vascular targeting with a tumor tissue endothelium-specific monoclonal antibody. TES-23, which strongly and selectively recognizes tumor tissue endothelial cells, was chemically conjugated with Neocarzinostatin (NCS), and the anti-tumor effect was examined. The immunoconjugate, TES-23-NCS, showed, through the use of tumor hemorrhagic necrosis, a marked antitumor effect on KMT-17 tumors in rats at a dosage of 17 mu g/kg (NCS equivalent) without any side effects, probably due to specific turner vascular injury. By contrast, TES-23 alone (107 mu g/kg), NCS alone (17 mu g/kg), and Mopc-NCS (Mopc, 107 mu g/kg; NCS, 17 mu g/kg), the immunoconjugate of control antibody, did not have any anti-tumor activities. By tissue distribution analysis, TES-23 and TES-23-NCS showed high accumulation in KMT-17 tumors 1 h after intravenous administration. Moreover TES-23 also accumulated in Sarcoma-180 tumors in mice 1 h after intravenous administration. These results suggest that TES-23 may be a candidate for a potential tumor vascular targeting agent that is applicable to a wide variety of tumor types. (C) 1999 Academic Press.