Hepatocyte growth factor (HGF) is a promoter of hair follicle growth. We examined another HGF family member, macrophage-stimulating protein (MSP), for its hair follicle-modulating properties. Western blotting revealed presence of mature MSP in cultured human dermal papilla (DP) cells and bulbar dermal sheath (DS) cells, but not non-bulbar DS cells. Immunohistology demonstrated expression of MSP receptor RON in the outer and inner root sheaths, hair matrix cells, DP, and bulbar DS whereas non-follicular epithelium and some cells of the sweat glands exhibited low-level receptor expression. Human hair follicles exposed in vitro for 8 d to 0.1, 1, 10, and 100 ng per mL MSP all yielded a mean net increase in hair follicle length in excess of the mean baseline growth observed in controls. MSP was incubated with agarose beads and injected subcutaneously into mice all 70 d old when a uniform telogen state in dorsal skin was apparent. All eight mice receiving 1 microg MSP, and four of eight receiving 100 ng MSP showed induction of anagen hair growth at the site of bead implantation by 16 d whereas eight mice implanted with saline incubated beads had no hair growth. The data identify MSP as a modulator of hair growth.