This study was performed to determine the role of nutritional status as a determinants of 5 fluorouracil (5-FU) toxicity in a tumor bearing mice. After subcutaneous inoculation, of mammary tumor (81 B) mice were assigned randomly to two nutritional regimens, (1) 8% casein: D-mice, (2) 27% casein: N-mice. Mortality was increased significantly in D-mice (100%) compared with N-mice (0%) by administration of 5-FU (20 mg/kg). Intratumoral 5-FU concentration of D-mice was significantly lower than that of N-mice, 1 hour after i.p injection of 5-FU (100 mg/kg, 300 mg/kg). Both growth rate and intratumoral protein content of transplanted tumor was equivalent in two dietary group, N-mice and D-mice. Protein depleted status was associated with a significant reduction in Interferon production of spleen cells. Inhibition of cell proliferation in bone marrow and cytokine production were recognized in hypo-nutritional status. Thus, improved nutritional status reduced the morbidity and mortality associated with 5-FU treatment in tumor bearing mice.