The extent to which hydromorphone, clonidine, and oxazepam alleviate the symptoms of opioid withdrawal and the extent and pattern of self-administration of these drugs during methadone detoxification were examined within a residential laboratory in three groups of patients dependent on methadone. Six times over the course of detoxification, acute effects of orally administered placebo and a single active drug (hydromorphone HCl, 3 mg, clonidine HCl, 0.3 mg, or oxazepam, 30 mg, all given twice daily) were tested, followed by an opportunity for subjects to self-administer the drug and dose of their choice. Hydromorphone significantly decreased opioid withdrawal symptoms and was more preferred for self-administration than the placebo. Clonidine and oxazepam did not significantly decrease withdrawal symptoms, nor was either drug self-administered significantly more than placebo. Clonidine, however, did induce side effects.