Two patients with acute onset of profound weakness and loss of muscle bulk during a critical illness had unusual histopathological changes of type II myofibers. Both patients had respiratory failure and prolonged neuromuscular blockade. High-dose steroids were used in only one case and atracurium in the other. Muscle biopsies at days 30 to 32 demonstrated widespread atrophy, basophilic cytoplasm, and vesicular nuclei, features suggestive of regeneration involving virtually all type II myofibers and sparing type I myofibers. This may be another variant of critical illness myopathy or a variation of the pathology during the course of illness.