The effects of the alpha-2 adrenergic agonist, clonidine, on the "quasi-morphine withdrawal syndrome" (QMWS) were examined in drug naive rats. The QMWS was induced by combined systemic administration of iso-butyl-methylxanthine (IBMX: 15 mg/kg, IP) and naloxone (1 mg/kg, IP). Pretreatment with clonidine (50 micrograms/kg, IP) significantly decreased the incidence of 11 out of 16 withdrawal signs. Since clonidine suppresses signs and symptoms of true morphine withdrawal, the suppression of methylxanthine effects demonstrates an additional similarity of the QMWS to true morphine withdrawal. These results suggest that a significant common neural mechanism of both the QMWS and true morphine withdrawal is affected by clonidine.