In many degenerative and metabolic muscle diseases cells die without a marked inflammatory response. A potential mechanism how this could be accomplished is apoptotic cell death. Since there are no data available about apoptosis in cells of myogenic origin, we examined rat skeletal myoblasts for their potential to undergo apoptosis when exposed to reactive oxygen intermediates and nitric oxide. We observed morphologic changes typical for apoptotic cell death, and DNA fragmentation was confirmed by gel electrophoresis and molecular labeling assays. With these methods we could show that both reactive oxygen intermediates and nitric oxide can induce apoptosis in myoblasts in a dose-dependent manner. These results are discussed with regard to possible implications on the pathophysiology of various muscle diseases.