Evidence mounts favoring the relationship, albeit unexplained, between Clostridium septicum infection and malignancy, particularly hematologic or intestinal malignancy. Seven patients with C. septicum gangrene or sepsis have been treated at the Massachusetts General Hospital in the years 1977-79. All of these patients have had associated malignant disease: four patients had colon adenocarcinomas, two patients had acute myeloblastic leukemias, and one patient had breast carcinoma. In six of the seven patients, the malignancy was in an advanced state; the breast carcinoma showed no evidence of recurrence after mastectomy, 17 years earlier. A bowel portal of entry is postulated in five patients. Despite prompt use of appropriate antibiotics, the only survivors were two of the four patients who underwent early extensive debridement. These results suggest that, in the patient with C. septicum infection, malignancy should be sought; that, in the septic patient with known malignancy, C. septicum should be considered; and that, in the absence of external source in the patient with clostridial myonecrosis or sepsis, the cecum or distal ileum should be considered a likely site of infection. Increased awareness of this association between C. septicum and malignancy, and aggressive surgical treatment, may result in improvement in the present 50-70% mortality rate.