Opioid abuse is common in Iran. In 2005, a new version of locally produced illicit opioid vials, so called Norgesic, appeared in the illicit market, which gained popularity rapidly and led to an improvement of stigmatizing the general appearance of dependent cases. Later, some cases suffered Cushing's-like problems. A prospective case series was designed to evaluate 18 Norgesic-dependent subjects who volunteered for abstinence therapy in a rehabilitation clinic from November 1, 2005, to December 30, 2005. In this study, we aimed to describe the clinical and paraclinical findings in detail and define the potential determinants of this Cushing's syndrome outbreak. History, physical examination, plasma cortisol level, and urine screen tests were used to describe the patients. All subjects were male with a mean (SEM) age of 29.8 +/- 1.6 years. The opioid-dependence period was 8.4 +/-0.9 years. In an average of 4.7 +/- 0.3 months, subjects increased their usage to 5.5 +/- 0.5 vials a day. Patients claimed to gain weight. Striae were seen in 38.9%, previously documented psychological problems in 33.3%, weakness in 27.8%, high systolic blood pressure in 22.2%, moon face in 16.7%, hirsutism in 11.1%, extensive dermal infection in 11.1%, gynecomastia in 5.6%, back pain in 5.6%, insomnia in 5.6%, and lack of potency in 5.6%. Their cortisol level, on average, was 4.8 +/- 1.1 microg/dL. Hepatitis C virus was positive in 22.2%. Urine-screening tests were positive for morphine and negative for buprenorphine. In conclusion, these new vials contain steroids as well as opioids. This combination could be more dangerous than opioids themselves.