Hepatocyte growth factor-scatter factor (HGF-SF) is a pleiotropic cytokine with mito-, morpho-, and motogenic effects on a variety of epithelial and endothelial cells. HGF-SF activity is mediated by the c-met protooncogene, a membrane-bound tyrosine kinase. Here, we demonstrate that both genes are expressed in developing and adult mammalian brains. HGF-SF mRNA is localized in neurons, primarily in the hippocampus, the cortex, and the granule cell layer of the cerebellum, and it is also present at high levels in ependymal cells, the chorioid plexus, and the pineal body. c-met is expressed in neurons, preferentially in the CA-1 area of the hippocampus, the cortex, and the septum, as well as in the pons. In the embryonic mouse, brain HGF-SF and c-met are expressed as early as days 12 and 13, respectively. Neuronal expression of HGF-SF is evolutionary highly conserved and detectable beyond the mammalian class. Incubation of septal neurons in culture with HGF-SF leads to a rapid increase of c-fos mRNA levels. The results demonstrate the presence of a novel growth factor-tyrosine kinase signaling system in the brain, and they suggest that HGF-SF induces a functional response in a neuronal subpopulation of developing and adult CNS.