Prostaglandin (PG) E(2) promotes osteoclastic cell differentiation, but the physiological function of PGF(2alpha) remains unclear. We examined the physiological effects of PGF(2alpha) on osteoclast differentiation using a murine cell line, RAW264, and the column-purified murine bone marrow cells, both of which are differentiable into osteoclast-like multi-nuclear cells. Although PGF(2alpha) did not affect the number of differentiated osteoclasts, PGF(2alpha) reduced the bone resorption activity of osteoclasts developed from both cell types in a pit formation assay. Thus, PGF(2alpha) inhibits bone resorption without affecting the number of osteoclasts, providing a novel molecular mechanism underlying bone metabolism.