Among the differentiated progeny of stem cells transplantable by bone marrow are osteoclasts, the multinucleate cells which are the major agents of bone resorption. Although the osteoclast is well characterized from a structural and functional standpoint, its development and origin are still far from clear. We have used monoclonal antibodies to investigate the interrelationship between osteoclasts and other haemopoietic cells in man. We have analysed the distribution of 19 granulocyte-monocyte antigens in eight reactivity clusters on the non-neoplastic osteoclasts present within nine osteoclastomas (syn. giant cell tumours of bone) and a single example of aneurysmal bone cyst. We found that osteoclasts are antigenically effete, failing to express granulocyte-monocyte, common leucocyte or other haemopoietic determinants; the only monocyte antigens detected on osteoclasts are My-7 and two closely related specificities, MCS.2 and DüHL60.4, which are also expressed by tissues outside the haemopoietic system. Our findings, taken together with recent transplantation studies, cast further doubt on the view that osteoclasts are specialized bone-resorbing macrophage-derived giant cells, and support a hypothesis that they are the end product of fusion of a hitherto unidentified circulating mononuclear cell type, the preosteoclast, which constitutes a cell lineage separate from those originating from the conventional multipotential haemopoietic stem cell, although still of bone marrow origin.