The defective gene responsible for Duchenne muscular dystrophy in humans and the dystrophic condition in mdx mice results in a lack of dystrophin at first thought to be localized to the triads, but more recently found on the cytoplasmic side of the sarcolemma of skeletal muscle fibres^1–5. Because the total calcium content of dystrophic fibres is significantly raised^6–9, we have compared the intracellular free calcium concentration ([Ca²⁺]_i) in skeletal muscle in normal and mdx mice. We find that [Ca²⁺]_i is markedly elevated in mdx muscle fibres compared with normal fibres, both at rest and during stimulation. By measuring protein degradation rates and manipulating [Ca²⁺]_i, we have been able to demonstrate directly that the elevation of [Ca²⁺]_i in mdx fibres results in an enhanced net degradation of muscle proteins.