α-Dystroglycan, a 156 kDa dystrophin-associated glycoprotein, binds laminin in skeletal muscle. Here we demonstrate that α-dystroglycan is a binding protein of laminin (A/B1/B2) and merosin (M/B1/B2) in peripheral nerve. Immunocytochemical analysis demonstrates the localization of α-dystroglycan and merosin surrounding myelin sheath of peripheral nerve fibers. Biochemical analysis demonstrates that the 120 kDa peripheral nerve α-dystroglycan binds merosin as well as laminin. The binding of laminin and merosin is Ca²⁺ dependent and is inhibited by NACl and heparin. Recently, merosin was shown to be deficient in the peripheral nerve of dy mice which have defects in myelination. The interaction between α-dystroglycan and merosin may play a role in the regulation of Schwann cell myelination and/or maintenance of myelin sheath.