Osteomyelitis caused by anaerobic bacteria is rarely reported, and a case of chronic osteomyelitis of the femur may be the first in which Clostridium difficile was the causative agent. The organism was isolated over several months and, although initially sensitive to penicillin, it developed resistance during this time. The organism's repeated isolation may have been due to the presence of resistant spores. Although the patient had no gastrointestinal symptoms the source of the organism was probably the patient's own gastrointestinal tract. Infection from the environment cannot, however, be excluded. Treatment was finally successful with metronidazole.