The organization in the brainstem of descending pathways of spinal inhibition was examined in the lightly pentobarbital-anesthetized rat. Thresholds for focal electrical stimulation-produced inhibition of the spinal nociceptive tail flick (TF) reflex were determined at one stimulation site in the midbrain periaqueductal gray and three sites in the rostral medulla: nucleus raphe magnus, and the adjacent medullary reticular formation contralateral and ipsilateral to the stimulating electrode in the periaqueductal gray. Lidocaine (0.5 microliter, 4%) was subsequently microinjected in the same and other medullary loci in the same coronal plane to produce a time-limited, reversible functional neural block. The functional block produced by 0.5 microliter of lidocaine microinjected in the medulla was determined to have a radius of 0.5 mm and was maximally efficacious during the first 30 min after its intramedullary microinjection. The stimulation threshold in the periaqueductal gray for inhibition of the TF reflex was not increased significantly when either the nucleus raphe magnus was fully blocked by lidocaine microinjected in three dorsoventral positions 1.0 mm apart or when the medullary reticular formation ipsilateral and contralateral were simultaneously fully blocked. Not until the nucleus raphe magnus and medullary reticular formation ipsilateral were simultaneously blocked by lidocaine was the stimulation threshold in the periaqueductal gray for inhibition of the TF reflex significantly increased. An increase in the periaqueductal gray stimulation threshold twice as great resulted when the nucleus raphe magnus and both the ipsilateral and contralateral medullary reticular formations were all simultaneously blocked by lidocaine. These results indicate that: (1) the nucleus raphe magnus is not a necessary bulbar relay in a descending antinociceptive pathway activated by stimulation in the midbrain periaqueductal gray; and (2) descending inhibitory pathways activated in the periaqueductal gray course medially as well as laterally in the rat ventral medulla.