Opioid-receptor-active material, endorphins, has been measured in cerebrospinal fluid samples obtained from schizophrenics. A chromatographic procedure isolated the Fraction I endorphin which was quantitated in a receptorassay. At least two cerebrospinal fluid samples were obtained from each patient, at Day 0 with no medication and at Days 30 and 60 after medication with fluphenazine under standardized conditions. Three series of patients were included: acute schizophrenics (= 11); re-entry schizophrenics (n = 7) who have previously been treated with neuroleptics but were readmitted to hospital usually as a consequence of stopped medication, and chronic schizophrenics (n = 9) who had been without neuroleptics for at least 2 weeks prior to Day 0. At Day 0, 6/9 acute cases, 4/6 of re-entry and 2/9 chronic cases had endorphin levels above the range of healthy volunteers. The levels in chronic cases were significantly lower than those in acute cases. Treatment with neuroleptics significantly lowered the endorphin levels in acute cases. These results confirm and extend previous observations.