The effect of thyrotropin releasing hormone (TRH) on the development of tolerance to the analgesic and hyperthermic actions of morphine was determined in male Sprague-Dawley rats. The tolerance to morphine was induced by subcutaneous implantation of 6 morphine pellets, each containing 75 mg of morphine free base. Rats serving as controls were implanted with 6 placebo pellets. Subcutaneous injections of TRH (1, 3 or 10 mg/kg) twice a day for 7 days inhibited the development of tolerance to the analgesic, but not to the hyperthermic action of morphine. Doses lower than 1 mg/kg or greater than 10 mg/kg administered twice a day for 7 days did not modify tolerance development. The inability of higher doses of TRH to inhibit tolerance to morphine may be related to rapid down-regulation of TRH receptors. The results suggest that in appropriate doses, TRH can selectively inhibit the development of tolerance to the analgesic action of morphine.