We studied beta-spectrin using an immunologic probe in muscle samples from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), other disease controls, and normal controls. By immunohistochemistry in DMD samples, beta-spectrin showed reduced or interrupted staining of the entire cell surface or only patches of bright staining at the cell periphery. There were also alterations of beta-spectrin immunostain in fibers that were not degenerating or regenerating. By immunoblotting, the amount of beta-spectrin in muscle was reduced and varied from 52% to 78% of the normal controls. We found normal values of beta-spectrin in BMD and disease controls. These observations indicate that the expression of beta-spectrin in DMD is abnormal and that beta-spectrin immunolabeling is not a good marker for monitoring membrane integrity in DMD muscle.