Intrathecally administered clonidine produces analgesia, but also produces hypotension. To assess the effects of epidural administration, the authors inserted lumbar epidural catheters in seven nonpregnant ewes, and injected, on separate days, clonidine (50-750 mcg), morphine (5-10 mg), and a clonidine-morphine combination (clonidine 150 mcg + morphine 5 mg). Clonidine produced dose-dependent antinociception and sedation, with the lowest maximally effective antinociceptive dose being 300 mcg. Morphine produced less intense antinociception than clonidine, and did not potentiate clonidine's effect. Antinociception, but not sedation, following clonidine injection was reversed by epidural injection of the alpha 2-adrenergic antagonist, idazoxan. Epidurally administered naloxone and prazosin did not reverse clonidine's antinociceptive effect, nor did intravenously administered idazoxan. Epidurally administered clonidine did not decrease blood pressure or heart rate or affect arterial blood gas tensions or spinal cord histology. These data suggest that epidurally administered clonidine produces analgesia by a local, alpha 2-adrenergic mechanism. In sheep, epidurally administered clonidine does not produce hypotension.