Endomorphins are opioid peptides which have potent analgesic and gastrointestinal effects. These effects are mediated by the activation of specific receptors. Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) are tetrapeptides with the highest known affinity and specificity for the μ opioid receptor. It is assumed that endomorphins are the cleavage products of a larger precursor, but this polypeptide or protein has not yet been identified. At the cellular level, endomorphins activate G-proteins and inhibit calcium currents. Endomorphin-1 (EM-1) is more widely and densely distributed throughout the brain while endomorphin-2 (EM-2) is more prevalent in the spinal cord and lower brainstem. EM-1 and EM-2 are two highly selective m-opiate receptor agonists. Intense EM-2 immunoreactivity is present in the terminal regions of primary afferent neurons in the dorsal horn of the spinal cord and in the medulla.