Protein(s) found in supernatants of macrophage cultures has been found to be toxic to several different tumor cell lines in vitro and recent results indicate that this protein is arginase. In response to injection to tumor cells, the intracellular content of macrophage arginase also increases. Implantation of chambers with attached tumor cells into mice also increases the arginase content of the extracellular fluid and it has been shown that the arginase originates in the macrophages. Most solid tumors contain many macrophages. Evidence has been accumulating suggesting that malignant cells require more arginine for growth than normal cells and it has been proposed that a reduction in arginine content of the microenvironment around the tumor is a defense mechanism to control tumor growth. It is proposed to study the role of macrophage arginase in toxicity to various tumors. We are purifying the arginases of mouse liver and macrophages. We will reduce antisera to the arginase and with these antisera, we will determine the cell type responsible for arginase production and determine whether the increase in this enzyme is due to increased syntheses, decreased secretion or some other mechanism. We are isolating the factors from fetal calf serum that are responsible for the in vitro stimulation of arginase of peritoneal macrophages. The effect of various prostaglandins and cyclic nucleotides on the productions of arginase is being investigated.