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To investigate hepatocyte growth factor (HGF) concentration in cerebrospinal fluid (CSF) in neurologic disease. We determined CSF concentration of HGF with human-HGF-specific enzyme-linked immunosorbent assays (ELISA) in 121 patients: Alzheimer's disease (AD) (33), amyotrophic lateral sclerosis (ALS) (10), Parkinson's disease (PD) (5), progressive supranuclear palsy (PSP) (3), spinocerebellar degeneration (7), acute disseminating encephalomyelitis (ADEM) (6), human T-lymphotropic virus-1 (HTLV-1)-associated myelopathy (HAM) (6), multiple sclerosis (MS) (7), aseptic meningitis (AM) (12), and peripheral neuropathy and myopathy as control diseases (32). HGF concentrations in CSF were significantly higher with diseases of the central nervous system (CNS) than control diseases and were slightly higher with AD than other neurodegenerative diseases. Values were highest with ADEM but decreased during corticosteroid treatment. We found no relationship between HGF in CSF and CSF cells or protein, immunoglobulin index, or Q albumin. It is suggested that high concentrations of HGF in CSF may be partially related to CNS pathology, especially to demyelinating disease.