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The origin of macrophages was studied in mouse radiation chimeras by chromosome marker technique. Macrophage cultures were established from peritoneal exudate, from lung washings, and from organ cultures of bone marrow, spleen, lymph node, thymus, and lung. Cultured macrophages were induced to divide by adding conditioned medium from L cell cultures. In chimeras which were lethally irradiated and given injections of bone marrow or spleen cells, dividing macrophages were of donor type, independent of the source of the macrophages. When chimeras were established by injections of a mixture of bone marrow cells and cells from other hematopoietic tissues of two genetically different donors, the ratio of cells with different genotypes was approximately the same in bone marrow cells and in macrophage cultures. Thymus, lymph node, and peritoneal exudate cells were not found to contain precursor cells for macrophages. Precursor cells for macrophages and for bone marrow cells appeared to be equally sensitive to sublethal irradiation. The results indicate that macrophages from different sources can all be derived from hematopoietic tissues, and suggest that only hematopoietic tissues contain precursor cells for macrophages which are capable of in vitro division. The close relationship between the source of cells in bone marrow and in macrophage cultures suggests that, at the maturation level at which the irradiated host is repopulated, the precursor or stem cells for macrophages may be identical with those for myeloid and erythroid series of cells.
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