Control C57Bl/10 and mutant, dystrophin-deficient mdx mice of different ages were used to study the permeability of the plasma membrane to cytosolic components, to a vital stain (procion orange) and to extracellular 45calcium. Prenecrotic, 14 +/- 2-day-old mdx mice had normal serum activities of creatine kinase (CK) and pyruvate kinase (PK). Muscles from these animals also had no increased permeability to procion orange or extracellular 45calcium. Serum activities of CK and PK had risen acutely in the 21-day-old mdx mouse compared with control and remained elevated up to 6 months of age. The influx of procion orange and 45calcium content were abnormally elevated in the 40 +/- 4-day-old mdx mouse. These data provide no evidence for an increase in muscle plasma membrane permeability as a primary pathogenic effect of a lack of dystrophin, but results suggest that some factor expressed or de-expressed during mouse development may be necessary for the full expression of the dystrophic process.