ß-Endorphin1-31 is released from the pituitary into the bloodstream during exercise but its peripheral roles in functioning skeletal muscle are only just beginning to be elucidated. These roles include increasing the glucose uptake into skeletal muscle, possibly by an insulin-independent mechanism, and decreasing muscle fatigue during strenuous contractions. The effects of ß-endorphin 1-31 on glucose uptake could be mimicked by ∂-opioid ligands (with amino acid sequences resembling the N-terminal sequence of ß-endorphin 1-31) or by peptides derived from the ß-endorphin C-terminal, whilst the effects on fatigue could be reproduced by ß-endorphin C-terminal derivatives but not by ∂-opioid ligands. The potency of ß-endorphin 1-31, and its derivatives was different in males and females. It seems likely that ß-endorphin 1-31 is a pleiotrophic hormone by virtue of the actions of its different peptide sequences. ß-Endorphin receptors are present in muscles of normal rodents where they are restricted to the neuromuscular junction, and               ß-endorphin immunoreactivity could be demonstrated in motoneurone terminals, indicating that the hormonal effects of the circulating peptide may be augmented by nerve-derived peptides. ß-Endorphin receptors are present along the entire muscle membranes in obese-diabetic mice or dystrophic mice and ß-endorphin immunoreactivity is extremely high in motor nerves in these conditions. ß-Endorphin 1-31 and a C-terminal derivative increased glucose uptake in muscles of obese-diabetic mice or dystrophic mice and their effect on muscle fatigue was demonstrated in dystrophic mice. Thus ß-endorphin 1-31 or stable synthetic C-terminal derivatives of this peptide might be useful in the treatment of glucose-intolerant or muscle-wasting conditions.