Proliferative monocytes (PMs) contain precursors of tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cells (MNCs). Non-proliferative (NP) and PM subpopulations from 13 donors, sorted as in Figure 1, were cultured in duplicate or triplicate cultures in macrophage colony-stimulating factor (M-CSF) (8,000 U/mL) and receptor activator of nuclear factor-kappa-B ligand (RANKL) (50 ng/mL) for 21 days; because insufficient cells were available, the two starting populations from fewer donors were also cultured in M-CSF alone. TRAP+ MNCs were counted. The mean number of such cells was significantly higher in the PM-derived cells cultured in M-CSF and RANKL compared with the NP-derived population (*P < 0.001). M, macrophage colony-stimulating factor; R, receptor activator of nuclear factor-kappa-B ligand.