Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes, and also has multifunctional effects on some other cells in various organs. A HGF activating protease, HGF activator (HGFA) has recently been identified as a key enzyme that regulates the activity of HGF in vivo. HGFA appears to be associated with the cell surface. We examined HGFA immunolabelling in the brains of neurologically normal and Alzheimer disease (AD) cases. Furthermore, we identified the expression of the mRNA for HGF and HGFA by in situ hybridization histochemistry. The HGFA antibody stained only astrocytes in the white matter in all the brain tissues. Expression of the mRNAs of HGF and HGFA was also seen in white matter astrocytes. These results suggest that, in human brain, secreted pro-HGF from astrocytes might be activated by HGFA on/or near the astrocytic cell surface.