Acridine orange-RNA fluorescence in diagnostic muscle biopsies is a sensitive, specific method to identify single fibers undergoing neurogenic atrophy. Fibers thus identified may be clearly distinguished from nonfluorescent type-specific atrophic fibers, as well as from atrophic fibers encountered in other myopathic conditions. Regenerating fibers, inflammatory cells, and mast cells stain prominently with acridine orange but area easily identified by their morphologic features. Acridine orange-RNA fluorescence is extremely useful in the evaluation of early neurogenic atrophy without fiber-type grouping and may be performed on paraffin-embedded sections, thus allowing retrospective studies. In addition, this technique may provide clues to the pathogenesis of neuromuscular disease that involves altered nucleic acid metabolism.