1. The effects that were induced by a beta-lipotropin fragment des-tyrosine-gamma-endorphin (DT gamma E) devoid of opiate activity that was administered intraperitoneally or intracerebroventricularly to mice under morphine analgesia were investigated. The interaction of this peptide with the analgesic effects of morphine was examined using the hot plate and the tail flick test. 2. Intraperitoneal acute treatment with DT gamma E did not change the analgesic effects of morphine. 3. Intraperitoneal semi-chronic treatment performed for 4 days with DT gamma E enhanced morphine analgesic effects. 4. The intracerebroventricular acute treatment with DT gamma E reduced morphine analgesia in a dose-dependent way. 5. These results indicate that DT gamma E, although devoid of opioid activity per se, may interact with the opioid system, probably through an indirect mechanism.