We report 2 patients with myonecrosis due to Clostridium septicum and associated colon carcinoma and have reviewed the English language literature for all reported cases of atraumatic C. septicum infection. A total of 162 cases of C. septicum infection have been reported. Eighty-one percent of these patients had an associated malignancy. Thirty-four percent of all patients had associated colon carcinoma, while 40% had a hematologic malignancy. Thirty-seven percent of reported patients had an occult malignancy at the time of their infection with C. septicum. In many patients, the portal of entry was found in the large intestine. In a particularly lethal form (79% mortality) of C. septicum infection, known as "distant myonecrosis," infection metastatic from the initial site of infection causes severe myonecrosis, gangrene, and often death within hours of clinical detection. Overall, survival of patients with C. septicum infection is only 35%. Review of all cases of C. septicum infection suggests several conclusions. 1) Patients with malignancy, particularly colonic or hematologic, and patients with cyclic neutropenia who develop signs and symptoms of sepsis, especially with associated findings of abdominal pain or pain in an extremity, should be treated for possible clostridial infection. 2) C. septicum infection does not appear to be a result of a single specific defect in either humoral or cell-mediated immunity. Rather, it may occur in patients who are granulocytopenic and therefore prone to an enterocolitis. 3) Patients in whom an infection with C. septicum is found must undergo a vigorous search for malignancy following acute therapy.(ABSTRACT TRUNCATED AT 250 WORDS)