Based on previous findings that liver zinc and metallothionein (MT) levels increase after tumor transplantation, zinc metabolism in tumor-bearing mice was studied to clarify the role of zinc-MT in host defense systems. Zinc in the hepatic cytosolic MT fraction did not increase in tumor-bearing mice fed a zinc-deficient diet, suggesting that dietary zinc is necessary for apo-MT induction in the liver after tumor transplantation and is then incorporated into the apo-MT. When (ZnCl2)-Zn-65 was intravenously injected, liver Zn-65 levels in the tumor-bearing mice were higher than those in central mice for 72 h after the injection. Pancreatic and blood Zn-65 levels in tumor-bearing mice were lower than those in controls for 24 h (pancreas) and 6 h (blood) after the injection. These findings indicate that the hepatic zinc response via MT induction influences zinc metabolism in the body after tumor transplantation. Moreover, Zn-65 uptake in the liver of MT-deficient tumor-bearing mice was lower than that in control tumor-bearing mice 1 h after injection. Zn-65 uptake in the tumor and blood Zn-65 levels in the MT-deficient tumor-bearing mice were higher than those in the control tumor-bearing mice. Tumor weight increased more in MT-deficient mice than in control mice, The formation of zinc-MT in the lives of tumor-bearing mice might decrease blood zinc availability for tumors and other tissues, such as the pancreas.