The in vitro culture of mouse bone marrow (Dexter cultures) has allowed a detailed analysis of the biology of murine hematopoiesis. However, attempts to develop stable long-term human bone marrow cultures have been unsuccessful. Available culture systems all have finite and relatively short lifetimes. The reasons for the limited longevity are unknown. Utilizing computer-assisted integration techniques, we have theoretically simulated culture cell production kinetics to help identify factors that may be responsible for culture decay, as well as to suggest possible means of improving culture longevity. The simulation demonstrates that removal of stem cells is a possible mechanism leading to culture decline. Under the standard bone marrow culture conditions, even with a high stem cell renewal rate, the cultures appear to be destined to fail. Thus, the development of proper sampling techniques or improved stem cell retention may be critical to obtain successful long-term cultures.