Opioid receptors are thought to be activated by endogenous peptides under physiologic conditions. These peptides, which include endorphins such as a-endorphin, enkephalins, and dynorphins, are synthesized in the cell body and are transported to the nerve endings where they accumulate in synaptic vesicles. On release from nerve endings, they bind to opioid receptors and can be displaced from binding by opioid antagonists. Endorphins have highest affinity for μ receptors, enkephalins for δ receptors, and dynorphins for κ receptors. Although it remains unclear whether these peptides function as classic neurotransmitters, they appear to modulate transmission at many sites in the brain and spinal cord and in primary afferents. Opioid peptides are also found in the adrenal medulla and neural plexus of the gut.