Using PCR, hepatocyte growth factor (HGF) and c-met (HGF receptor) expression were analyzed in the developing mouse kidney. Both HGF and c-met were expressed from Gestational Day 11.5 onward, the time at which branching morphogenesis of ureteric bud occurs. Coculturing the embryonic kidney with MDCK cells seeded in Type I collagen induced branching morphogenesis of the MDCK cells. When a monospecific antiserum against HGF was included in the culture medium, the branching morphogenesis induced by the embryonic kidney was markedly inhibited (73%). This anti-HGF serum also inhibited metanephric growth when incubated with 11.5- to 12.5-day embryonic kidneys in an organ culture assay. No inhibition was observed by nonimmune serum. Perturbation of ureteric duct development as well as extraductal metanephric development was observed in embryonic kidneys incubated with the anti-HGF serum. Together, our data indicates an important role for HGF in kidney development.