The endogenous opioid peptides have multiple physiological actions at both a central and peripheral level which are mediated by 3 main classes of opioid receptors, mu, delta and kappa. The rat mu, delta and kappa opioid receptors have recently been cloned and their distribution of expression in the central nervous system has been mapped. In these studies we have used the reverse transcriptase polymerase chain reaction and Southern blotting to determine the distribution of expression of the mu, delta and kappa opioid receptors in the peripheral tissues of the rat. All 3 opioid receptors were found to be widely expressed in several peripheral tissues including the small intestine, large intestine, adrenal, kidney, lung, spleen, testis, ovary and uterus. In the stomach, delta and kappa but not mu opioid receptor transcripts were detected. Predominantly delta transcripts were detected in the heart, with no mu and only a weak signal for the kappa receptor. In the liver mu and delta but not kappa transcripts were present. Opioid receptor expression was not detected in endothelium or synovium. There is therefore a broad, but tissue specific distribution of opioid receptor expression in the periphery of the rat, suggesting that the endogenous opioid peptides play an endocrine, paracrine, or autocrine role in the regulation of physiology at a peripheral as well as central level.