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Macrophage colony-stimulating factor (M-CSF) has been previously shown to facilitate the in vitro survival and differentiation of mononuclear phagocytes. We assessed whether M-CSF administration in vivo could induce macrophages capable of killing tumor via an antibody-dependent mechanism. C57BL/6 mice were given intraperitoneal M-CSF, and peritoneal macrophages were assayed for their ability to kill fluorochrome-labeled Rl.l thymoma cells in vitro in the presence or absence of target-specific antibody. Two-color flow cytometry was used in measuring tumor ingestion by macrophages; macrophages from M-CSF-treated mice eliminated > 90% of Rl.l thymoma target within 24 hours, while macrophages from saline-treated controls were ineffective. Rl.l tumor elimination by macrophages depended on the presence of target-specific antibody. These are the first studies that demonstrate the in vivo induction, by M-CSF, of macrophages directly capable of ingesting antibody-conjugated tumor cells.