It is now known that there are three principal families of opiate peptides that are present in high concentration in the hypothalamus. These derive from three separate large precursor proteins: preproenkephalin, preprodynorphin and preproopiomelanocortin. Post-translational enzymatic cleavage of these proteins gives rise to the enkephalins, dynorphin and β-endorphin. Large numbers of enkephalin-producing neurons are found in many hypothamic nuclei, and these are the most widely distributed of the opioid peptides throughout both the hypothalamus and the extrahypothalamic C.N.S. It is now know that within the hypothalamus, particularly in the paraventricular nucleus, enkephalinergic. neurons also produce corticotropin releasing factor (CRF). Direct pathways from these hypothalamic neurons containing enkephalin follow several different routes, for example, from the paraventricular nucleus to the brain stem and spinal cord. The highest concentration of dynorphin in the nervous system is found in the hypothalamus, and probably the most important cells containing it are within the arcuate nucleus. The distribution of dynorphin resembles that of vasopressin, and it is probable that most vasopressin-containing neurons also produce dynorphin. In the arcuate nucleus, it is likely that dynorphin co-exists with dopamine. The hypothalamus is also the principal site of endorphin production.