The secretion of the macrophage and granulocyte inducer (MGI), also known as colony-stimulating factor (CSF), by epithelial cells from lungs and kidneys, and by fibroblasts from lungs, was determined as a function of time in culture; it was found to be secreted during the initial exponential proliferation period, and not when the cells approached saturation density. When the cells were again induced to proliferate, large amounts of CSF were released after 3 h, thus hinting at the existence of a reserve pool. A CSF activity of 70,000 daltons was found in cultures of fibroblasts from lungs, kidneys, and the peritoneal cavity, a 45,000-dalton CSF was obtained from mouse peritoneal macrophages, and from bone marrow cells when activated for macrophage proliferation, and a 22,000-dalton CSF was found from epithelial cells, thus suggesting that the different CSFs are cell specific. When fibroblast CSF was used to induce bone marrow cells, three new molecules with colony-stimulating activity were produced, of 45,000, 30,000, and 17,000 daltons. The fraction with the 17,000-dalton activity also contained interleukin 1 activity, hinting at an indirect induction of colony formation by this factor. Finally the possible existence of a cascade reaction in which one CSF induces the appearance of other CSFs during the normal regulation of myeloid cell differentiation is discussed.