To compare the analgesic efficacy and plasma concentration of intramuscular (IM)versusepidural (EP) clonidine, 20 patients recovering from orthopedic or perineal surgery were randomly divided into two groups of ten. Clonidine (2 μg/kg) was administered epidurally in group 1 and intramuscularly in group 2. Analgesia was assessed using a visual analog scale (VAS) over a period of 6 h following clonidine administration. Venous blood samples were obtained at specific intervals for radioimmunoassay determination of plasma clonidine concentrations. The maximum reduction in VAS pain score was 78.5 ± 20.6% in the EP group and 68.1 ± 31.5% in the IM group (NS). Onset of analgesia was similar (within 15 min of injection), but duration tended to be longer after epidural than intramuscular administration (208 ± 87 minvs.168 ± 95 min, mean ± SD,P> 0.05). The peak plasma clonidine concentration after EP injection was 0.82 ± 0.22 ng/ml and 1.02 ± 0.76 ng/ml after IM injection. Hypotension, bradycardia, and drowsiness occurred with both methods of administration. None of these effects required treatment. Thus, in postoperative patients clonidine produces similar analgesia and side effects after parenteral or EP administration.