There is evidence that muscle fibers in denervating disorders and muscular dystrophies undergo apoptosis. In 21 patients with autoimmune inflammatory myopathies, we found no features of muscle fiber apoptosis such as DNA fragmentation or expression of apoptosis-related proteins. However, muscle fibers in myositis displayed distinct up-regulation of inducible and neuronal nitric oxide synthase (NOS). While inducible NOS was distinctly up-regulated on the sarcolemma of all kinds of muscle fibers neuronal NOS displayed increased expression in the sarcoplasm of damaged as well as atrophic muscle fibers. There were no disease-specific patterns in the different myositis subtypes. Enhanced expression of NOS with production of nitric oxide may contribute to oxidative stress mediating muscle fiber damage and muscle fiber necrosis representing the predominant cell death mechanism in myositis. Nevertheless, inflammatory cells displayed numerous DNA-fragmentation-positive nuclei and expression of apoptosis-related proteins indicating that apoptosis plays a role in the regulation of the inflammatory cellular response.