The effects of chronic morphine treatment on beta-endorphin (betaE)-immunoreactive (betaE-ir) peptide levels were determined in the rat caudal medulla and different areas of the spinal cord. Seven days of morphine pelleting had no effect on total betaE-ir peptides in the caudal medulla. In contrast, it significantly increased betaE-ir peptide concentrations in the cervical and thoracic regions of the spinal cord compared with placebo-pelleted controls, whereas in the lumbosacral region this trend did not reach statistical significance. Injections of the opiate receptor antagonist naloxone 1 h before the rats were killed had no effect on the morphine-induced increases in the cord. Chromatographic analyses revealed that enzymatic processing of betaE-related peptides in the spinal cord seemed unaffected by the morphine and/or naloxone treatments. In light of previous data showing that morphine down-regulates betaE biosynthesis in the hypothalamus, the present results suggest that the regulation of betaE-ir peptides in the spinal cord is distinct from that found in other CNS areas. These data provide support for previous results suggesting that betaE-expressing neurons may be intrinsic to the spinal cord.