To examine the clinical value of 28-kDa calbindin-D (CaBP) in cerebrospinal fluid (CSF) as a marker for the damage to Purkinje cells, we measured CSF CaBP levels using an enzyme immunoassay method in 107 patients with cerebellar and other neurological diseases, and 26 controls. The mean CaBP level was markedly elevated in patients with cerebellar diseases, and the elevation of CaBP level was more frequent in the diseases involving Purkinje cells, such as multiple system atrophy (MSA) and subacute cerebellar degeneration in association with lung cancer. Further, in MSA patients, the CaBP levels decreased with duration of illness. The mean levels of CaBP were also elevated in some of the other diseases. We conclude that the elevations of CaBP levels are not specific for cerebellar diseases, but CSF CaBP may be a useful marker for examining the Purkinje cell involvement in cerebellar diseases.