The effects of d-fenfluramine and morphine on various nociceptive responses of rats were investigated. Unlike morphine, which inhibited all the responses examined, d-fenfluramine inhibited jumping and paw licking of rats on a hot plate, but did not increase the latency of tail withdrawal from hot water. The effects of d-fenfluramine on both responses on the hot plate were prevented by pretreatment with metergoline, a serotonin antagonist, whereas this pretreatment only reduced the effect of morphine on paw licking. The inhibition of tail withdrawal by morphine was also significantly reduced by metergoline treatment. The results confirm previous findings suggesting a role of serotonin in the mechanism by which morphine inhibits some nociceptive responses in rats. They also show that d-fenfluramine, a selective releaser and uptake inhibitor of serotonin at nerve endings, does not completely reproduce the antinociceptive effects of morphine in this species.