We have reported results which suggest that macrophages play an important role in prevention of tumor development, and in the inhibition or killing of tumor cells in vitro. We propose to study further the role of the monocyte-macrophage system in resistance to tumors in animal models and to determine the importance of this cell system in resistance to tumors in man. Experiments will be performed to determine the role of both the cytostatic and cytocidal effects of activated macrophages and how these functions contribute to resistance to cancer. The ability of lymphocytes or their products to bolster (or suppress) the cytotoxic effects of activated macrophages will be studied and we will employ synchronized target cell cultures to explore whether certain phases of the cell cycle are more sensitive than others to the cytostatic and cytocidal effects of activated macrophages. The methods and mechanisms whereby macrophages from different anatomical compartments can be preferentially activated will be determined, and we will study the cytotoxic effects of macrophages from these compartments, including macrophages from the tumor itself. In humans we will study in vitro peripheral blood monocytes and monocyte-derived macrophages, as well as tissue macrophages from the spleen to determine their effects on established lines of normal and neoplastic human cell lines. Experiments will be performed to activate these human monocytes and macrophages in vitro to kill tumor cells by culturing them in the presence of autologous lymphocytes (or lymphocyte products) and mitogens or antigen to which the individual has been shown to possess cell-mediated immunity and in the presence of soluble factors present in such lymphocyte culture supernatant medium.