Antinociception and central nervous system depression (CNSD) caused by intraperitoneal, intrathecal and subcutaneous administration of oxycodone or morphine were studied in a randomized and blind, saline controlled study in rats. Antinociception was assessed with the tail-flick and hot plate tests. CNSD was assessed by testing the corneal, placing and righting reflexes and with a 4-point catalepsy score. Intraperitoneally and subcutaneously administered oxycodone and morphine were given in doses of 2.5-10 and 5-20 mg kg-1 respectively. The intrathecal doses were 12.5 micrograms and 100 micrograms of oxycodone and 6.25 micrograms and 50 micrograms of morphine. In both nociceptive tests subcutaneously and intraperitoneally administered oxycodone was 2-4 times more potent than morphine, while intrathecal morphine was over 14 times more potent. CNSD was more profound with oxycodone than with morphine after intraperitoneal and subcutaneous administration, but was not observed after intratechal administration of either drug. Differences in opioid receptor affinities, liposolubilities and metabolism are discussed as possible explanations.