Clonidine hydrochloride (an alpha-2 adrenergic agonist) and naltrexone hydrochloride (an opioid antagonist), given in combination, provided a safe and effective treatment of abrupt opioid withdrawal over 5 days in an outpatient/day setting. Before starting the clonidine, a naloxone challenge test was used to verify and quantify opioid dependence, and the naloxone challenge test score was then used to determine initial medication doses. Initial naloxone challenge test scores predicted subsequent patient discomfort during the 5-day clonidine-naltrexone protocol. Twelve of 14 (86%) heroin users successfully withdrew from opioids and simultaneously initiated naltrexone maintenance.