Studies to elucidate changes in the contents of ulinastatin-like immunoreactive substance (UTIRS) and alpha 1-microglobulin-like immunoreactive substance (alpha 1 MIRS) in cerebrospinal fluid (CSF) of patients with dementia were performed. Levels of UTIRS in the dementia group were significantly (p < 0.01) lower than those in dementia-free subjects. In addition, lower levels of UTIRS were registered in subjects afflicted with a higher severity of dementia. However, the levels of alpha 1 MIRS were not affected in the dementia group compared with dementia-free subjects. Neither UTIRS nor alpha 1 MIRS contents were related to the existence and stages of Parkinson's disease. These results suggest that UTIRS levels in the CSF are associated with the severity of dementia.