C. difficile colitis ranges from mild diarrhea to life-threatening "toxic" illness with fever, severe diarrhea, and abdominal pain. A colitis, frequently with a pseudomembrone, is the characteristic finding on sigmoidoscopy and is caused by one of more toxins elaborated by the organism Clostridium difficile. The clinical syndrome is not specific and can be mimicked by other colonic infections, inflammatory bowel disease, radiation colitis, or ischemic colitis. The diagnosis should be suspected in any patient who develops diarrhea during antibiotic therapy or within 6-8 weeks of treatment. Diagnosis should be confirmed by the detection of C. difficile toxin in stool along with sigmoidoscopy or colonoscopy for special situations. Most patients will respond promptly to discontinuation of the antibiotic especially early. However, if the diarrhea persists or is severe of the patient appears to be ill, then specific antimicrobial therapy should be employed. Antimicrobial agents that have been shown to be effective in this syndrome include metronidazole and vancomycin. In some patients who do not respond to this therapy or have complications, subtotal colectomy may be required.