Pretreatment with receptor-activator of NFκB ligand (RANKL) permits osteoclastogenesis in the presence of maximally inhibitory IFN-γ in a dose-dependent and time-dependent manner. RAW cells were grown in the presence of continuous RANKL (100 ng/ml) for 4 days, in the absence or presence of IFN-γ as indicated on either day 0 or 2 of culture. (a) Representative photographs from each group are shown at 10× magnification, and (b) the average number of osteoclasts per well ± SEM is presented. (c), (d) The experiments were repeated with primary osteoclast precursors in splenocyte cultures. For both RAW cells and primary osteoclast precursors, RANKL pretreatment allowed for osteoclastogenesis despite the presence of a maximally inhibitory dose of IFN-γ (10 ng/ml). *P < 0.05 compared with either untreated controls or cells treated with IFN-γ for the whole culture period.