Radioimmunoassay procedures were used to assay levels of dynorphin A (DYN A) and substance P-like activity (SP) in cerebrospinal fluid (CSF) obtained from 10 schizophrenic patients before and after neuroleptic treatment, from 10 matched patients with other psychiatric disorders before and after treatment, and from 10 nonpsychiatric surgical controls. The highest mean concentration of CSF DYN A was found in the schizophrenic group on admission (significant vs. nonpsychiatric controls). The concentration remained almost unaltered after 4 weeks of zuclopenthixol treatment despite a highly significant decrease of overt psychopathology assessed by the Brief Psychiatric Rating Scale (BPRS). There was no significant difference between the mean CSF DYN A levels of the nonschizophrenic psychiatric patients and the surgical controls. When all psychiatric patients were pooled together, there was a significant correlation between the level of CSF DYN A and the BPRS total score. With regard to CSF SP levels, no statistically significant differences were observed within or between the groups studied. Neither was there a significant correlation between the concentration of CSF SP and overt psychopathology. Nevertheless, the mean CSF SP concentration of three patients with major depression was clearly higher than the corresponding mean concentration of the other patients in the nonschizophrenic group.