Clathrin-coated vesicles are involved in three receptor-mediated intracellular transport pathways: export from the Golgi apparatus, transfer of lysosomal enzymes from the Golgi apparatus to lysosomes, and endocytosis at the plasma membrane. Seeking evidence of transport abnormalities in distal myopathy with rimmed vacuoles (DMRV), we performed immunohistochemistry for clathrin in muscle biopsy specimens from patients with this disorder or other neuromuscular disorders, and also in control muscle samples resected in orthopedic procedures. While most myofibers from control muscle did not stain for clathrin, some fibers revealed finely granular sarcoplasmic staining. In specimens from patients with Duchenne and Becker muscular dystrophy, amyotrophic lateral sclerosis, peripheral neuropathy, and DMRV, numerous clathrin-positive granules were often scattered through the sarcoplasm and seen to a lesser extent in subsarcolemmal regions. Quantitative immunohistochemical assessment showed more reactivity for clathrin in DMRV than in controls and other diseased muscles, particularly in atrophic fibers and type 2 fibers. Not all strongly clathrin-positive muscle fibers contained rimmed vacuoles, although most fibers with vacuoles were clathrin positive. The result suggests that the lysosome system is activated and receptor-mediated intracellular transport pathways function appropriately in the muscles of DMRV patients.