While most would agree that the mid-seventies were vintage years for endor phin research, 1982 is certain to be" a very good year." Less obvious to the public eye, it is nevertheless a turning point in endorphin research, because it is the year in which all the brain opioids" found a home." Prior to that point we could count more than eight different endogenous ligands containing the opioid core Tyr-Gly-Gly-Phe-Met (or Leu). However, their relationships were un clear, and their anatomical distribution in the central nervous system (eNS) even less so. It was therefore impossible for the functionally minded neuro scientist to design and execute experiments taking this heterogeneity into consideration. Even pharmacological studies with these peptides were difficult to interpret in a physiological framework. In 1982, thanks mainly to the recombinant DNA techniques, we learned that all these peptides belong to three genetically distinct peptide families, as we describe below. We now know a great deal more about their anatomy, and we are beginning to clarify their biosynthetic pathways. Suddenly, we can think in terms of circuits rather than in" humors" or in black boxes. In our study of function, we can no longer ignore the multiple systems, any more than the student of monoamines can ignore differences between dopaminergic and noradrenergic systems. Less clear, but equally critical, is the issue of multiple opioid receptors. Unquestionably, the heterogeneity exists. What remains to be established is whether each of the three families of opioids has its own receptor, or whether a given family can interact with more than one SUbtype, and each receptor subtype with more than one family. More critical to physiology is whether