The effect of a recently described, potent opioid peptide, dermorphin (DER), on TSH secretion in euthyroid subjects has been studied. DER infused at a rate of 5.5 micrograms/Kg/min for 30 min induced a significant increase in serum TSH concentration at 60, 90, and 120 min after the infusion was begun. Treatment with naloxone administered 30 min before the DER infusion with a bolus dose of 4 mg, followed by a constant infusion of 1 microgram/Kg/min for 150 min, prevented the rise in serum TSH. Naloxone administered alone did not induce any change in TSH concentration. The present findings suggest that DER has a stimulatory effect on TSH secretion, probably mediated by opioid receptors. These results, however, do not solve the question as to whether opioids have a physiological role in the control of pituitary TSH secretion.