Opiate receptors, stereospecific binding sites on the end of free nerve endings that bind exogenous opioids, are localized in the ascending and descending pain pathways. These receptors mediate the multiple pharmacological effects of the opioid analgesics. Subpopulations of opioid receptors including high- and low-affinity µ receptors and γ, κ, and δ receptors are localized to specific areas of the brain, spinal cord, and peripheral nervous system. More recently, several opioid receptor subtypes have been cloned, and quantitative changes in the messenger RNA for these receptors have been determined in experimental models. The cloning of these subtypes of receptors that mediate different pharmacological effects and are then located in specific cerebral, spinal, and peripheral sites offers the possibility of developing new analgesics targeted for specific receptors. For example, µ receptors modulate predominantly supraspinal analgesia, whereas δ and κ receptors are important in modulating analgesia at the spinal cord level. The periaqueductal gray region in the midbrain and the dorsal horn in the spinal cord are rich in these receptors and are the supraspinal and spinal sites that mediate opioid analgesia. The use of brainstem and spinal cord stimulation and the administration of opioid analgesics directly into the cerebrospinal fluid, bathing the selective opioid sites in patients with cancer who are in pain, are procedures based on this knowledge. Pain transmission at the spinal cord level can be inhibited by the direct application of morphine onto the spinal cord, and these studies have led to the use of spinal opioid analgesia in clinical pain states.