The purpose of this study was to determine if there are alterations in the dihydropyridine and/or ryanodine receptors that might explain the excitation-contraction uncoupling associated with eccentric contraction-induced skeletal muscle injury. The left anterior crural muscles (i.e., tibialis anterior, extensor digitorum longus, and extensor hallucis longus) of mice were injured in vivo by 150 eccentric contractions. Peak isometric tetanic torque of the anterior crural muscles was reduced ~45% immediately and 3 d after the eccentric contractions. Partial restoration of peak isometric tetanic and sub-tetanic forces of injured EDL muscles by 10 mM caffeine indicated the presence of excitation-contraction uncoupling. Scatchard analysis of [³H]-ryanodine binding indicated that the number of ryanodine receptor binding sites was not altered immediately post-injury, but decreased 16% 3 d later. Dihydropyridine receptor binding sites increased ~20% immediately after and were elevated to the same extent 3 d following the injury protocol. Muscle injury did not alter the sensitivity of either receptor. These data suggest that a loss or altered sensitivity of the dihydropyridine and ryanodine receptors does not contribute to the excitation-contraction uncoupling immediately after contraction-induced muscle injury. We also concluded the loss in ryanodine receptors 3 d after injury is not the primary cause of excitation-contraction uncoupling at that time.