Vitamin D-dependent calcium-binding protein (Calbindin-D: CaBP) (MW 28 kDa) is present in high concentrations in the central nervous system (CNS), especially in the cerebellum. In the cerebellum, CaBP is localized in Purkinje cells. By using an enzyme immunoassay method, we measured the cerebrospinal fluid (CSF) levels of CaBP in 96 neurological patients and 24 control subjects, and evaluated the clinical usefulness of determining CaBP, especially in the diagnosis of cerebellar damage. CSF CaBP levels were strikingly elevated in patients with cerebellar lesions, including primary spinocerebellar degeneration (SCD), subacute cerebellar degeneration with lung cancer, Wernicke-Korsakoff syndrome, as well as in patients with cerebrovascular disease (CVD) without involvement of the cerebellum. In these 2 groups, neuron-specific enolase (NSE) levels were determined. The ratio of CaBP to NSE (CaBP/NSE) in patients with cerebellar lesions was higher than that in CVD, reflecting differences in lesions between these 2 groups. In the SCD group, multiple system atrophy (MSA) showed higher CaBP levels than the other types of SCD. Probably it reflects remarkable damage of the Purkinje cells in MSA. In MSA, the CaBP levels decreased with the duration of illness. In myelopathy, neuropathy, meningitis, multiple sclerosis, and other degenerative diseases, the increase of CaBP was not remarkable. Our results suggested that CSF CaBP is considered to be a marker of cerebellar damage.