The increasing number of observations implicating macrophages in the destruction of tumors, and the recent upsurge in the use of macrophage activators underline the importance of the study of characteristics of this cell in different stages of differentiation. We intend to analyze the capabilities of peritoneal macrophages obtained from normal mice or from mice which were injected with BCG, bacterial endotoxin, thioglycollate medium and other known macrophage activators in terms of (a) function of plasma membrane receptors for C3; (b) phagocytosis of opsonized particles; (c) ability to bind and kill tumor cells. We want to extend our preliminary observation that ingestion via the complement receptor is a marker for macrophage activation. We also plan to determine the role of complement in the induction of monocyte and macrophage differentiation, in addition to chemotaxis. The methods for the study of phagocytosis and tumor cell lysis are well denfined and currently in use in our and in other laboratories. Strains of mice with specific genetic defects such as the nude, deficient in T lymphocytes, and the C3H/HeJ which show no B-cell transformation by endotoxin will be used to elucidate the role of lymphoctyes in macrophage activation. The role of complement will be determined using cobra venom factor and purified C components "in vivo" and "in vitro". We expect to better define the phenomenon of macrophage activation, to understand the mechanism by which some macrophage activators function and to obtain basic clues on the process of recognition of tumors and of targets of phagocytosis. We will also define "in vitro" tests for macrophage activation which correlate with functional capabilities of the cell "in vivo".