The capacity of resident peritoneal macrophages and alveolar macrophages for self-renewal was studied in CD-1 mice depleted of radiosensitive blood monocyte precursors by irradiation of the bone marrow with the bone-seeking isotope 89Sr. Thermoluminescent dosimetry and studies of DNA synthesis showed that significant levels of radiation were absorbed predominantly in anatomical sites in close proximity to bone. Cell proliferation remote from bone marrow was unaffected when quantitated by DNA precursor uptake. Between 10 and 15 days after injecting mice intravenously with 89Sr at 2 microCi per gm. of body weight, monocytes were only rarely detectable in the peripheral blood as determined by morphology, stains for nonspecific esterase and peroxidase, and by latex phagocytosis. Total numbers of resident peritoneal and alveolar macrophages were not significantly decreased and tritiated thymidine incorporation in vivo persisted at normal levels rather than regressing at a predicted rate during profound monocyte depletion. The data, therefore, suggest that local proliferation by resident macrophages in monocytopenic and intact mice is an important mechanism of population renewal.