Studies have been made on the hypophysectomy-induced changes in antinociceptive and temperature responses to morphine and the effects various anterior pituitary hormones have on these altered responses under both acute and chronic conditions. Hypophysectomy altered the slope of the dose-response curve for morphine antinociception without significantly changing the ED50. It also induced an upward shift in the temperature-response curve. Treatment of hypophysectomized animals with s.c. adrenocorticotropic hormone decreased responsiveness to the antinociceptive and the hyperthermic actions of morphine. Administration of triiodothyronine increased the antinociceptive response and normalized the upward shift in the temperature response; however, these effects required approximately 3 weeks of hormone treatment. Both of these treatments normalized the altered antinociceptive dose-response curve slope. Growth hormone, luteinizing hormone and prolactin had no effects on acute morphine responses. Further experiments examined the effects of anterior pituitary hormones during chronic treatment with morphine. Adrenocorticotropic hormone, when administered 30 min before morphine, showed reproducible but statistically nonsignificant suppression of tolerance development. Growth hormone, which had no effects on acute morphine responses, was more effective than adrenocorticotropic hormone at suppressing tolerance. In studies with animals bearing growth hormone/prolactin secreting tumors, significant suppression of tolerance was seen for both responses to morphine. These results add further support to previous findings from our laboratory that the adrenal and thyroid systems are involved in modulation of acute opiate actions and also indicate that growth hormone can inhibit the development of opiate tolerance.