Abstract: Prevention of conditions, such as osteoporosis, requires an understanding of the molecular mechanisms of bone resorption. The understanding that cells of the myeloid lineage are osteoclast precursors suggests that macrophage colony-stimulating factor (M-CSF) plays an important role in osteoclast biology. Signals generated by the binding of M-CSF to the cell-surface receptor c-Fms appear to trigger events leading to osteoclast differentiation. We have created a chimeric variant of the c-Fms receptor, which has allowed study of downstream events activated by M-CSF in a model more relevant to normal physiology than prior studies, which have relied on myeloid tissues. Our studies suggest novel regulatory signaling pathways initiated via the c-Fms receptor.