These studies examine the mechanisms underlying the transition from granulocytes to macrophages that characterizes cultures of bone marrow cells. Normal mouse marrow was cultured for several weeks in diffusion chambers (DCs) implanted in previously irradiated host mice. Previous studies with this system have shown that there is a period of logarithmic cell growth for 7 d following by a plateau in both total cell number and the numbers of CFU-S and CFU-C. The present studies show that this plateau in cell growth is associated with high cycling rates of both CFU-S and CFU-C. The plateau phase ends with a rapid decrease in the numbers of these progenitor cells. This is associated with a decline in the number of granulocytes, whereas macrophages persist at approximately the plateau level for the entire 48 d of culture. Transplantation of plateau phase cells into secondary DC cultures leads to a more rapid decline in the numbers of CFU-S and CFU-C followed by the total disappearance of granulocytes; in contrast, macrophage number undergoes a small increase which is maintained thereafter. When regular injections of 3H-thymidine are given to host mice bearing late phase secondary cultures, macrophage labelling rises to a plateau of only 30-40%, indicating that most macrophages at this stage of culture are long-lived cells. The kinetics of the stem cell changes implicate the CFU-C as the immediate precursor of granulocyte development in DC cultures but suggest that the CFU-S is the major determinant of overall cell renewal in this system. Macrophages doubtless also originate from CFU-C but, unlike granulocytes, these are often long-lived cells probably with some capacity for continuing cell division. These properties account for the often observed propensity of macrophages to repopulate bone marrow cultures from which stem cells and granulocytes have been depleted.