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This study examined the hypothesis that descending inhibitory pathways from brain stem to spinal cord mediate the analgesic effect of both electrical brain stimulation and morphine. In the first set of experiments, the effect of subtotal midthoracic spinal cord lesions on the analgesic effect of electrical stimulation in the periaqueductal gray matter of the rat was examined. In the second, the effect of similar cord lesions on the analgesic effect of intraperitoneal morphine was studied. In both cases, a lesion of the dorsal part of the lateral funiculus (DLF) reduced or abolished the analgesia of the hindlimbs. Analgesia of the forelimbs was unaffected. Lesions of the dorsal columns, which include the corticospinal tract, or lesions of the ventral part of the lateral funiculus had no effect on analgesia. It is concluded that an inhibitory pathway, which descends in the dorsal part of the lateral funiculus and which probably originates in the nucleus raphe magnus of the medulla, mediates the descending control found in both morphine and stimulus-produced analgesia.