By means of tissue culture, electron microscopy, cytochemistry, indirect immunofluorescence and immunohistochemistry, the multinucleated giant cells(MGCs) in 12 giant cell tumors of bone (GCT) were studied in contrast with osteoclasts (OCs), foreign body giant cells (FGCs) and inflammatory giant cells (IGCs). The findings in the majority of MGCs were identical with those in OCs, suggesting that they most probably derived from the same precursor. Continuous in vitro culture revealed two kinds of MGCs, which were designated preliminarily as short-lived MGCs and long-lived MGCs for their difference in morphology and in several biological features, which suggests two kinds of MGCs exist in GCT. We conclude that the short-lived conform to the typical MGCs known generally to the pathologists, while the long-lived are deemed to be closely related to the neoplastic elements of the tumor.