The study by Van Furth and Cohn investigates the origin and turnover of mononuclear phagocytes in mice, focusing on circulating monocytes and tissue macrophages. Mononuclear phagocytes are categorized into two groups: circulating monocytes in the blood and tissue macrophages in organs such as the spleen, lymph nodes, liver, lungs, peritoneal cavity, and subcutaneous tissues. The primary function of tissue macrophages is to clear and destroy bacteria, foreign materials, and damaged tissue cells from the bloodstream, lymph, or outer environment. The fate and function of circulating monocytes are less understood, but they can mature into tissue macrophages both in vitro and in vivo. The study uses in vivo and in vitro labeling techniques with thymidine-3H to track the labeling patterns of peritoneal macrophages and blood monocytes. Key findings include: 1. **Peritoneal Macrophages**: These cells show a low turnover rate, with only a small percentage dividing under normal conditions. In response to inflammation, a rapid entry of blood monocytes into the peritoneal cavity is observed. 2. **Blood Monocytes**: These cells originate from the bone marrow and are rapidly released into the circulation. The turnover rate of blood monocytes is high, with a half-life of about 22 hours, indicating a random exit from the circulation. 3. **Origin of Monocytes**: Splenectomy and X-irradiation experiments suggest that the spleen is not a major source of blood monocytes, and that the bone marrow is the primary site of production. Bone marrow cultures show a pool of rapidly dividing mononuclear phagocytes, which are the progenitors of blood monocytes. 4. **Kinetics of Monocytes**: The initial rate of monocyte appearance in the peripheral blood is 1.7% per hour, with a maximal turnover time of 40 hours. The half-life of monocytes is 22 hours, suggesting a random exit from the circulation. 5. **Discussion**: The study concludes that mononuclear phagocytes follow a unidirectional flow from the bone marrow to the peripheral blood and then to the tissues, where they differentiate into macrophages. The ultimate fate of tissue macrophages remains to be determined, but they may either senesce and die or re-enter the circulation. The study provides a detailed understanding of the life cycle and dynamics of mononuclear phagocytes in mice, highlighting the role of the bone marrow as the primary source of these cells.The study by Van Furth and Cohn investigates the origin and turnover of mononuclear phagocytes in mice, focusing on circulating monocytes and tissue macrophages. Mononuclear phagocytes are categorized into two groups: circulating monocytes in the blood and tissue macrophages in organs such as the spleen, lymph nodes, liver, lungs, peritoneal cavity, and subcutaneous tissues. The primary function of tissue macrophages is to clear and destroy bacteria, foreign materials, and damaged tissue cells from the bloodstream, lymph, or outer environment. The fate and function of circulating monocytes are less understood, but they can mature into tissue macrophages both in vitro and in vivo. The study uses in vivo and in vitro labeling techniques with thymidine-3H to track the labeling patterns of peritoneal macrophages and blood monocytes. Key findings include: 1. **Peritoneal Macrophages**: These cells show a low turnover rate, with only a small percentage dividing under normal conditions. In response to inflammation, a rapid entry of blood monocytes into the peritoneal cavity is observed. 2. **Blood Monocytes**: These cells originate from the bone marrow and are rapidly released into the circulation. The turnover rate of blood monocytes is high, with a half-life of about 22 hours, indicating a random exit from the circulation. 3. **Origin of Monocytes**: Splenectomy and X-irradiation experiments suggest that the spleen is not a major source of blood monocytes, and that the bone marrow is the primary site of production. Bone marrow cultures show a pool of rapidly dividing mononuclear phagocytes, which are the progenitors of blood monocytes. 4. **Kinetics of Monocytes**: The initial rate of monocyte appearance in the peripheral blood is 1.7% per hour, with a maximal turnover time of 40 hours. The half-life of monocytes is 22 hours, suggesting a random exit from the circulation. 5. **Discussion**: The study concludes that mononuclear phagocytes follow a unidirectional flow from the bone marrow to the peripheral blood and then to the tissues, where they differentiate into macrophages. The ultimate fate of tissue macrophages remains to be determined, but they may either senesce and die or re-enter the circulation. The study provides a detailed understanding of the life cycle and dynamics of mononuclear phagocytes in mice, highlighting the role of the bone marrow as the primary source of these cells.