Pharmacologic studies of analgesia produced by stimulation of the nucleus locus coeruleus (LC) were conducted using the rat hot-plate test. A correlation between self-stimulation and analgesia produced by stimulation of LC was found. Analgesia produced by LC stimulation was attenuated by naloxone, a morphine antagonist, cyproheptidine, a serotonin antagonist, and WB-4101, an alpha-adrenergic antagonist. The analgesia was absent in 6-OHDA-treated rats. Catecholamine synthesis inhibition by a combination of reserpine and AMT or more specific inhibition of noradrenaline synthesis by DDC elevated latency to paw lick and yet did not affect stimulation-produced analgesia. It is suggested that morphinergic, serotonergic, and alpha-adrenergic mechanisms mediate LC stimulation produced analgesia.