In Duchenne muscular dystrophy, muscle cells, which lack the protein dystrophin, have been reported to have elevated resting intracellular calcium levels. It has also been noted that, compared to normal muscle, intracellular [Ca²⁺] in dystrophic muscle returns more slowly to its resting level following contractile stimulation. Consistent with this, it has been suggested that dystrophin is directly involved in the regulation of Ca²⁺ influx. A secondary alteration in the sarcoplasmic reticulum Ca²⁺ pump, however, could also contribute to, or be responsible for, the abnormal Ca²⁺ handling seen. To determine whether the Ca²⁺ pump is functionally altered in dystrophic muscle, we examined Ca²⁺ uptake by vesicles derived from skeletal muscle sarcoplasmic reticulum of normal and dystrophic (mdx) mice. The Hill coefficient and the Ca²⁺ sensitivity of the Ca²⁺-ATPase were the same in both cases. The maximum velocity of Ca²⁺ uptake, however, normalized to the ATPase content of the vesicles, was less for mdx muscle.