Clinical prospects of an analog of thyrotropin-releasing hormone (DN-1417) and des-tyrosine-gamma-endorphin (DT gamma E) in schizophrenia were examined by using the Brief Psychiatric Rating Scale (BPRS) and the electroencephalogram (EEG). Twelve inpatients with chronic schizophrenia were administered fixed doses of neuroleptics throughout the study. Six patients were treated with DN-1417 (DN-1417 group), and the remaining 6 patients with DT gamma E (DY gamma E group). One mg/day of DN-1417 or DT gamma E was given intramuscularly for 2 consecutive weeks followed by 1 week of no drug treatment. In the DN-1417 group, both total BPRS scores and scores on hallucinatory behaviour and unusual thought content decreased in the first and third weeks. The power values of alpha and beta activities from the frontal area increased in the first and third weeks, whereas an increase in alpha activity and a decrease of high-fast beta activity from the occipital area were obtained during the study. On the other hand, the DT gamma E group failed to show either a decrease in BPRS scores or any remarkable EEG changes except for a slight decrease in beta activity. These results suggest that the positive symptoms of schizophrenia are improved by DN-1417 treatment, and that the alterations in BPRS scores coincide with changes in the frontal EEG.