Long-term bone marrow culture is an experimental in vitro model of hematopoiesis imitating conditions in vivo. It contains hematopoietic elements at various stages of differentiation as well as a supportive stromal microenvironment. Primitive hematopoietic stem cells of mesenchymal origin, the long-term culture initiating cells proliferate and differentiate into different cell types, giving rise to the adherent stromal layer and to various hematopoietic elements attached to it or floating freely in the supernatant medium. The stromal layer keeps the hematopoietic cells aggregated, helps their mitosis, differentiation and maturation by cell-to-cell contact, produces hematopoietic growth factors (cytokines), and forms the extracellular matrix required for cell attachment. Hematopoiesis occurs without exogenous growth factors. The appearance and development of the stroma, the proliferation and differentiation of hematopoietic progenitor cells, and the production of cytokines differ in long-term cultures of the normal and of pathologically altered bone marrow. Long-term bone marrow culture is applied in fundamental studies of normal and pathologically altered hematopoiesis, in pharmacological research, in the purging of residual leukemia cells from bone marrow autotransplants, and in the gene transfer. It is also suitable for testing carcinogenic and toxic chemicals causing hematopoietic damage through occupational or habitual exposure.