The acute effects of peripherally administered methysergide or phentolamine on the analgesic activity of salmon calcitonin (sCT) injected into the lateral ventricle were investigated in male rats. Methysergide, but not phentolamine, significantly (P less than 0.05) antagonized the analgesic activity of sCT at 60 and 120 min after the administration of the peptide. The results obtained suggest that the analgesic activity of sCT may involve central serotonergic system(s), while the central noradrenergic system does not seem to be needed for this activity.