In the present report osteoclast formation from cloned pluripotent hemopoietic stem cells (PHSC) is described. Populations enriched in hemopoietic stem cells were cloned (1 cell/well) and cultured in the presence of different colony-stimulating factors, or combinations of these growth factors. In cultures containing interleukin-3 (Il-3) or pregnant mouse uterus extract (PMUE) alone, cloning efficiency was low. Cultures containing Il-3 and Il-1 or Il-3 and PMUE showed a somewhat higher cloning efficiency, whereas cultures containing Il-3, Il-1 and PMUE had the highest cloning efficiency. All colonies of cloned PHSC, tested for their osteoclast formation capability in cocultures with periosteum-free metatarsal bones of fetal mice, gave rise to osteoclast formation. Other hemopoietic cells could also be demonstrated. In control cultures in which the bones were kept without stem cells, no osteoclast formation was observed. In conclusion, we have demonstrated that the osteoclast is derived from the pluripotent hemopoietic stem cell. A combination of various growth factors is important for stem cell proliferation in vitro.