• Reports of an antiwithdrawal effect for clonidine hydrochloride in acute opioid withdrawal are inconsonant with experimental findings that other nonopioids are ineffective. In the present investigation the antiwithdrawal effects of clonidine, morphine sulfate, and placebo were compared in volunteer addicts whose dependence was maintained by 15 mg of morphine sulfate given subcutaneously four times daily. Clonidine was effective but had a differential effect on the signs and symptoms of morphine abstinence. Compared with morphine, clonidine was more effective in suppressing autonomic signs of abstinence but less effective in reducing subject-reported symptoms and discomfort. It is concluded that the perception of the clinical usefulness of clonidine depends on whether objective measures or subjects' reports are treated.