The chloride channel ClC-1 is required to maintain a normal excitability of mature muscle fibers; its blockade leads to hyperexcitability, the hallmark of the disease myotonia. In mouse and rat myotubes, representing the embryonic stage of muscle, ClC-1 mRNA is not detectable by Northern blotting. From neonatal to adult, ClC-1 expression increases at least fourfold. Using RT-PCR and hybridization on cultured myotubes we found ClC-1 mRNA at a level of 0.4-1.1% of that in mature mouse muscle, and less than or equal to 0.01% in myoblasts, at stages when desmin mRNA levels are already high. The level of ClC-1 mRNA is thus a sensitive and specific indicator of the maturation of skeletal muscle cells.