To elucidate the mechanisms of analgesic action of elcatonin, a synthetic analog of eel calcitonin, the effect of centrally injected elcatonin on acetic acid-induced writhing behavior was examined in mice. Intracisternal or intracerebroventricular injection of elcatonin significantly inhibited acetic acid-induced writhing behavior, while the intrathecal injection of elcatonin did not inhibit it. The inhibitory effect of intracisternal elcatonin was significantly attenuated by subcutaneous pretreatment with methysergide and (+/-)-propranolol or by intrathecal pretreatment with methysergide, (+/-)-propranolol, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl]-piperazine hydrobromide (NAN-190) and granisetron, but not with (+/-)-atenolol or butoxamine. Further, the depletion of spinal 5-hydroxytryptamine (5-HT, serotonin) by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT) significantly attenuated the inhibitory effect of intracisternally injected elcatonin on acetic acid-induced writhing behavior. These results suggest that the inhibitory descending serotonergic systems may be involved, through 5-HT1A and 5-HT3 receptors, in the production of an antinociceptive effect by centrally injected elcatonin.