A 10-y-old female rhesus macaque presented acutely with 3 large (diameter, greater than 4 cm), malodorous, ulcerogangrenous skin wounds on the left caudal thigh and calf. Limb radiographs revealed free gas infiltrating deep tissues, and histologic examination confirmed myonecrosis. Clostridium perfringens, Staphylococcus aureus, and Prevotella intermedia were isolated from the wounds. Antimicrobials, analgesics, and aggressive debridement of necrotic skin and muscle resulted in immediate clinical improvement of the primate. At 1 wk prior to presentation, the animal had received several intramuscular injections in close proximity to the site of infection. Repeated intramuscular injections through excrement-contaminated skin possibly contributed to the pathogenesis of infection. Continued therapy consisted of biweekly wound debridement and nonadherent bandage changes for 7 wk. The macaque regained full use of the affected leg and remains in good physical condition at our facility. Our management of this case led to improvements in training regarding intramuscular injection practices in our macaque colony. This case study is the first report of Clostridium perfringens myonecrosis in a laboratory nonhuman primate. We discuss various methodologies for the diagnosis and treatment of necrotizing clostridial infections.