Metatarsal bone rudiments taken from 12- to 17-day-old mouse embryos were cultivated as organ cultures and/or transplanted on to the chorioallantoic membranes of Japanese quail embryos, with or without the adhering surrounding mesenchyme. In cultivated explants the presence of mesenchyme was essential for the development of osteoclasts. This mesenchyme contained small blood vessels. In transplants with adhering mesenchyme, graft (mouse)-derived osteoclasts predominated, whereas in transplants without surrounding mesenchyme the osteoclasts originated from host (quail) cells. Distinction could be made between mouse- and quail-derived osteoclasts because of the specificity of the chromatin pattern of quail cell nuclei. Precartilaginous anlagen of metatarsals precultured before transplantation, displayed mouse-derived osteoclasts, thus indicating that osteoclast progenitor cells home into the long bone anlage very early, in this case at least 6 days before the appearance of osteoclasts in vivo. During embryonic development, osteoclast progenitor cells could very well be (as in the adult situation) hematopoetic cells conveyed to the site of long bone development by the circulating blood as soon as distribution of these cells starts from central blood-cell forming organs to the periphery. Mesenchyme in and around the long bone region seems to play a role as early deposition site of these cells where proliferation, differentiation, and fusion of osteoclast progenitor cells take place and are controlled.