See article by Millington et al. ([1], pages 107–116) in this issue. In this issue Millington et al. [1] describe the localization of pro-opiomelanocortin (POMC) message and peptide products in adult and neonatal rat heart. These authors are to be commended for delving into the esoteric area of cardiac endocrine function and opioid peptides. The finding of atrial natriuretic peptide and opioid peptides in cardiac myocytes confirms the ability of the heart to participate in homeostasis beyond simple pumping. Consideration can now be given to the endocrine function of the heart. Besides POMC, proenkephalin and prodynorphin have been identified in heart and cardiomyocytes of different species including rodents, cat, dog, pig and humans [2–6]. The questions then arise: Why do muscle cells make opioid peptides? What are their functions? How are opioid peptides regulated in the cardiac myocyte? Before examining these questions a brief review of opioid peptide biochemistry may be helpful. The proenkephalin family of opioid peptides is used as an example. The proenkephalin sequence contains four copies of methionine-enkephalin (met-enk), one of leucine-enkephalin and two extended forms of met-enk (met-enk-arg-gly-leu and met-enk-arg-phe [MERF], Fig. 1). These small peptides are delineated for processing from the precursor by pairs of basic amino acids. Proenkephalin processing is achieved by prohormone convertases, which are endoproteolytic enyzmes recognizing the dibasic amino acids. Proenkephalin has an early cleavage to peptide B and later cleavages to other intermediate sized products that can finally be cleaved to the penta- to octapeptides [7,8]. Fig. 1 Preproenkephalin A and products isolated from adrenal medulla (adapted from Ref. [9]). The molecular weights are for the peptide beneath the number. SP, signal peptide; M, met-enkephalin; L, leu-enkephalin; M+, met-enk-arg-gly-leu; M*, met-enk-arg-phe. Sequences of processing and enzymatic conditions in nerves may differ from parenchymal tissue resulting in different products. Neural … * Tel.: +1-817-7352484; fax: +1-817-7355084