A 72-year-old woman on immunosuppressive therapy for renal transplantation was admitted to the hospital for diffuse, progressive weakness that developed over several weeks. Serum creatine kinase steadily increased and she developed myoglobinuria. Blood cultures were positive for group A Streptococcus pyogenes. The muscle biopsy demonstrated a necrotizing myopathy without cellular infiltrate. Despite treatment, she evolved to multiorgan system failure and cardiovascular collapse. This is a novel presentation of group A streptococcal muscle infection with diffuse, generalized muscle weakness. It stands in striking contrast to the usual infection with this organism confined to one extremity and associated with a prolific cellular response in the muscle.