Calcium (Ca) and magnesium (Mg) content were determined in muscle of 27 patients with Duchenne muscular dystrophy, 36 with other neuromuscular diseases, and 22 whose muscle biopsy specimens were histochemically normal. Muscle Ca was significantly elevated in all diseases studied but was about 50% higher in Duchenne dystrophy patients (p < 0.0001). Mg was decreased by 44% in Duchenne dystrophy, compared with less striking deficits in other diseases (p < 0.005). In older, nonambulatory Duchenne dystrophy patients, Mg was significantly lower than in younger, ambulatory patients (p < 0.001); muscle Ca was the same in both groups. On the basis of noncollagen nitrogen concentration, muscle Mg depletion could not be attributed solely to reduced muscle mass. These findings strengthen arguments for a role of Ca in the pathogenesis of muscular dystrophy and may implicate Mg depletion as another pathogenetic factor.