In inclusion body myositis, T cells invade and destroy nonnecrotic muscle fibers. The mechanism by which T cells damage muscle fibers in inflammatory myopathies is not known. In this study we have investigated the expression of Fas and Fas ligand in muscle in five patients with inclusion body myositis. Reverse transcription polymerase chain reaction showed upregulation of both Fas and Fas ligand in all inclusion body myositis patients. Immunohistochemical investigation showed expression of Fas ligand in many of the muscle infiltrating mononuclear cells. Fas was expressed both in mononuclear cells and on the surface of muscle fibers in inclusion body myositis patients and in patients with polymyositis but not in patients with Duchenne muscular dystrophy or denervation. The results indicate that the Fas/Fas ligand system may be of importance for the inflammatory reaction and T-cell-mediated muscle cell injury.