Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional polypeptide that acts as a mitogen, motogen, or morphogen, depending on the biologic context. In this study, we examined the effect of HGF/SF on hair growth using a serum-free organ culture system. Vibrissal hair follicles isolated from newborn mice were cultured at 31 degrees C in 95% O2/5% CO2 for 72 h in the presence of various cytokines or growth factors, and elongation of hair shaft, DNA, and protein synthesis in hair follicles were measured. Among the agents tested, only HGF/SF significantly increased hair follicle length (p < 0.001), 3H-thymidine (p < 0.001), and 35S-cysteine (p < 0.05) incorporation. The effect of HGF/SF was dose dependent, with maximal stimulation obtained at 10 ng/ml. The increase in hair follicle length and thymidine incorporation were specifically inhibited by a neutralizing antibody against HGF/SF. These results indicate that HGF/SF can promote hair growth and may have clinical utility in this regard.