The intrathecal (IT) injection of serotonin in the rat was found to produce a variety of behavioral signs of the serotonin "syndrome" as well as intense gnawing. Serotonin-induced gnawing is qualitatively similar to that evoked by tail pinch. Paradoxically, tail pinch-induced gnawing has been previously shown to be inhibited by serotonergic activity while we found a positive dose-related correlation between the IT administration of serotonin and gnawing. Pretreatment with methysergide IT completely blocked gnawing produced by intrathecally injected serotonin but not that evoked by tail pinch. In contrast, naloxone, reported to inhibit tail pinch-induced hyperphagia, failed to affect serotonin-induced gnawing. The parenteral injection of haloperidol inhibited both tail pinch-induced and serotonin-induced gnawing. Failure of intrathecally injected haloperidol to inhibit serotonin-induced gnawing indicates that dopamine mediates this behavior at a supraspinal level. The ability of serotonin to elicit gnawing when injected at the spinal cord level, but to inhibit the same behavior when evoked by tail pinch, suggest that this neurotransmitter plays opposite roles depending on which part of the CNS is involved.