The proposed study will establish a new method for the study of hematopoietic stem cell proliferation and differentiation in a compartmentalized physiological environment. We will study in vivo both erythrocytic and granulocytic colony formation in a plasma clot-diffusion chamber culture system. Normal rat bone marrow cells seeded into chambers implanted into normal hosts show erythroid colony numbers reaching a peak on day 2; a secondary growth phase occurs on day 7 with colonies grouped into a "burst" arrangement. Granulocyte colonies reach a peak on day 4. Having established the pattern of colony growth in normal rats, perturbation of donor as well as host animals will provide information on the proliferative potential of committed stem cells. The culture system also allows for pretreatment of marrow cells prior to chamber seeding so that the nature of colony progenitors directly exposed to physiological regulators and/or cytotxic agents can be further examined. The proposed study, therefore, will attempt, using a new method, to investigate: the properties of hemic stem cells; the associations which exist between progenitors; the effects of humoral control substances, and the development of progeny cells within the competitive complexities of the hematopoietic system.