Ornithine decarboxylase activity in the livers, spleens, and kidneys of tumor-bearing mice changed markedly during tumor growth. These changes in enzyme activity were not due to infiltration or metastasis of tumor cells in these organs. After i.p. inoculation of Ehrlich tumor cells, enzyme activity in the liver and spleen increased remarkedly, reaching a peak in 4 to 6 days and then quickly decreasing. Conversely, activity in the kidney, which was very high in normal mice, decreased markedly during tumor growth, nearly reaching zero on Day 6 and remaining very low until death. Upon injection of a cell-free homogenate of Ehrlich tumor or cell-free ascites fluid, enzyme activity in the liver and spleen also increased markedly, but that in the kidney did not change. These increases in activity were not due to the effects of living tumor cells. Similar increases in enzyme activity were also observed in the livers of mice given injections of homogenates of Sarcoma 180 or Act. S tumor, or plasma from tumor-bearing mice, but not in the livers of mice given injections of homogenates of various nontumorous tissues, such as liver, kidney, spleen, muscle, regenerating liver, and fetus, or plasma obtained from normal mice. A similar increase in enzyme activity in the liver after injection of a cell-free preparation of tumor cells was observed in hypophysectomized and adrenalectomized mice; thus, these endocrine systems are probably not involved in the increase in enzyme activity in the livers of tumor-bearing mice.