A 17-year-old girl with chronic abdominal pain had low serum cortisol levels with a subnormal response to adrenocorticotropic hormone (ACTH) stimulation test while receiving opioid analgesics for pain. After discontinuation of the opioid analgesics, the cortisol levels returned to normal and repeated ACTH stimulation tests showed normal response of the hypothalamic-pituitary-adrenal (HPA) axis. A concise review of the literature on the effects of opioids on serum cortisol levels and the HPA axis is presented.