Morphine-, methamphetamine- and cocaine-induced place preferences under inflammation produced by unilateral injections of 2.5% formalin (50 microliters) and 1% carrageenan (100 microliters) into the hind paw were examined in rats. Formalin and carrageenan reduced the paw pressure threshold, and this hyperalgesia lasted for 9 and 13 days, respectively. Morphine-, cocaine- and methamphetamine-induced place preferences were significantly attenuated in inflamed groups as compared with the respective noninflamed groups. However, indomethacin failed to produce a place preference in either group. Furthermore, the morphine-induced place preference in the inflamed group gradually recovered to the respective control level as the inflammation healed. These results suggest that the rewarding effects of morphine, cocaine and methamphetamine are attenuated in the presence of inflammatory nociception.