We compared orosomucoid levels in cerebrospinal fluid (CSF) in patients with aseptic meningitis, multiple sclerosis, ischemic and hemorrhagic stroke, CNS-affecting leukemia/lymphoma, and CNS-tumor with the levels in a reference group not having neurologic diseases. Because of possible blood brain barrier damage, we corrected for orosomucoid derived from serum by using the orosomucoid index, i.e. (CSF/serum orosomucoid)/(CSF/serum albumin). Elevated CSF orosomucoid was found in several diseases. In no case, however, was there any evidence of intrathecal synthesis of the protein. We concluded that CSF orosomucoid determination, when used as the only, measure, is of limited clinical value.