The antitumor activity of a high molecular weight pro-drug of mitomycin C(MMC), MMC-dextran conjugate (MMC-D), was examined against various murine tumors under different experimental conditions. A single intraperitoneal injection of MMC-D exhibited higher antitumor activity against intraperitoneally inoculated B16 melanoma, Ehrlich ascites carcinoma, and P388 leukemia than MMC, but lower activity against BDF1 mouse-transplanted L1210 leukemia. Intratumoral injection of MMC-D showed a superior effect on subcutaneously implanted B16 melanoma, while intravenous injection of MMC-D exhibited reduced activity against P388 and L1210 leukemia compared with MMC. Prior administration of MMC-D at 24 hr before tumor inoculation resulted in a significant increase of the life span of mice bearing L1210 leukemia, suggesting that it shows sustained pharmacological activity. These differences between the activities of MMC-D and MMC in various tumor systems are considered to reflect the improved biopharmaceutical properties of MMC-D resulting from the modification of MMC into a polymeric drug.