Neuropeptide Y-like immunoreactivity (NPY-li) was measured in CSF of 35 drug-free chronic schizophrenic patients. Compared to a group of drug-free controls, CSF NPY-li was significantly higher in these patients. CSF NPY-li decreased with age and longer duration of illness. Measures of structural brain abnormalities on CT scans were significantly associated with lower CSF NPY-li. Relationships between NPY-li and schizophrenic behavior, i.e. positive symptoms, were observed only in the clinically stable (nonrelapsed) drug-free patients. In 31 of the patients CSF was obtained before and after withdrawal from haloperidol maintenance treatment. This withdrawal from haloperidol treatment was associated with a significant increase in CSF NPY-li. There was no significant difference in CSF NPY-li between patients who did and those who did not relapse within 6 weeks following haloperidol withdrawal. The present findings suggest a relationship of CSF NPY-li with various aspects of schizophrenia.