Plasminogen activator inhibitor-1 (PAI-1) is a serpin proteinase inhibitor which regulates fibrinolysis and the proteinase cascade of tumour invasion. In this study, PAI-1 was identified in the cerebrospinal fluid (CSF) from patients without neurological disease and patients with various neurological disorders. The mean level of PAI-1 in the CSF of 28 patients without central nervous system (CNS) disease was 0.28 +/- 0.03 (SEM) ng/ml. CSF PAI-1 was significantly increased in the following diagnostic categories:dementia (Alzheimer's disease), cerebral infarction, CNS infection, alcohol withdrawal seizures and CNS neoplasia. In all these disorders, with the exception of CNS infection, PAI-1 was also increased as a fraction of total CSF protein. CSF PAI-1 was not increased in patients with hydrocephalus or idiopathic seizure disorders. Complementary plasma samples were available for 18 of the 128 CSF specimens studied. For these cases, there was no correlation between plasma PAI-1 and CSF PAI-1 levels. PAI-1 may represent a non-specific marker of disease in the central nervous system.