One systemic effect of burn trauma is skeletal muscle weakness. This is the result of changes in second messenger systems involving calcium (Ca2+). Kinetic analysis of Ca2+ from cellular compartments of skeletal muscle of mice that were subjected to small burn injury (20% body surface area) was performed. Muscles of the burn group showed an increased 45Ca2+ uptake maxima compared with those of time-matched control groups. Also, 45Ca2+ efflux analysis showed a lack of differentiation between electrically stimulated tissues and nonstimulated tissues that was easily observed in time-matched control groups. This lack of differentiation indicated changes in intracellular compartmentation. It can be speculated that burn trauma may have a regulatory role in the excitation-contraction coupling mechanism by altering myoplasmic levels of Ca2+ even before skeletal muscle dysfunction occurs. These findings suggest that agents capable of controlling myoplasmic Ca2+ levels may aid in alleviating chronic skeletal muscle dysfunction in patients with burns.