We compared the muscle pathology and clinical course in eight patients with congenital nemaline myopathy. An abundance of large intranuclear rods was present in the muscle fibers of one patient with a rapid, fatal course. Intranuclear rods were not present in the muscles of seven patients with a benign course. The large intranuclear rods and the smaller sarcoplasmic rods were similar ultrastructurally and exhibited positive immunoperoxidase staining with anti-β-actinin antibodies. The accumulation of β-actinin within myonuclei may reflect a severe disturbance of normal intracellular processes regulating myofibrillar synthesis. Since two previously reported infants with intranuclear nemaline rods also had a fatal outcome, the presence of intranuclear rods may represent a marker for a severe form of congenital nemaline myopathy.