The pro-opiomelanocortin-derived peptides β-endorphin (β-EP) and α-melanocortin (α-MSH) were administered to normal and dystrophic C57BL6J mice. All groups of normal and dystrophic mice which had been treated with the two peptides gained significant body weight, as did the normal and dystrophic saline-treated male controls, but the normal and dystrophic female controls did not. The plasma activity of creatine phosphokinase (CPK) was lower in normal mice and dystrophic males which had been treated with the two peptides compared to the corresponding controls. There was no significant difference between the plasma LDH activity in any of the peptide-treated and the corresponding control groups. The activity of CPK was significantly higher in the extensor digitorum longus (EDL) muscles, but not the soleus muscles, of the peptide-treated dystrophic mice compared to the corresponding controls. Administration of α-MSH alone or β-EP alone had no significant effect on the body weight or plasma CPK activity of dystrophic mice compared to the controls. However the activity of CPK was significantly higher in the EDL muscles of the α-MSH-treated mice than in the corresponding controls It is possible that β-EP and α-MSH act synergistically on the neuromuscular system to protect the muscles from damage.