Clonidine HCl is an antihypertensive that is also sometimes used to alleviate symptoms of withdrawal during narcotics detoxification. Recently, there have been reports abuse of clonidine by methadone patients and opioid abusers. The present study evaluated the intravenous self-administration of clonidine in four baboons. Self-injections were available 24 h/day under a fixed-ratio (FR 120 or 160) schedule of injection with a 3-h timeout after each injection. Doses of clonidine (0.0001-0.056 mg/kg per injection) or its vehicle (saline) were substituted for cocaine (0.32 mg/kg) for at least 15 days. Food pellets were available continuously under a concurrent FR 30 schedule of pellet delivery. Clonidine maintained self-injection greater than its saline vehicle in all four baboons. Although self-injection of clonidine increased as a function of dose within each baboon, there were differences between baboons in the range of doses of clonidine that maintained self-injection. Doses of 0.032 or 0.056 mg/kg maintained peak mean levels of clonidine self-injection which ranged from low (3.2 injections/day) to high (> 6 injections/day) across baboons. Levels of self-injection were similar to vehicle at 0.01 mg/kg clonidine in two of four baboons. However, in the other two baboons, very low doses of clonidine (0.0001-0.001 mg/kg) maintained low to moderate levels of self-injection. Acute administration of clonidine produced signs of sedation including lip droop, drooling and sitting with eyes closed. At high doses, some toxicity was apparent: Baboons were pale and not responsive. Food intake was generally increased in a dose dependent manner. The present study indicates that clonidine functions as a positive reinforcer.