We have come to understand the cause of antibiotic-associated pseudomembranous colitis (PMC) only in the last decade. Clostridium difficile produces the intestinal dysfunction and the characteristic finding of exudative plaques on the mucosa by elaborating a toxin in the colon. This report reviews the development of our knowledge of this disease and the rapid adoption of a rational therapy once the cause was specified. C. difficile or its toxin can be cultured or isolated from the stools of 90% of the patients with PMC. This organism is almost never found in healthy people or in any other conditions except inflammatory bowel disease, where its significance is not yet known. The detection of pseudomembranes by sigmoidoscopy establishes the diagnosis. The laboratory technics that confirm the presence of C. difficile and its toxin are being incorporated into many laboratories around the country. Treatment of diagnosed PMC is relatively simple and usually completely effective. The offending antibiotic is stopped, a proper fluid and electrolyte balance maintained, and oral vancomycin begun, 125 to 500 mg four times a day. Cholestyramine can also be used as an adjunct to this regimen. Relapse can occur in patients treated with oral vancomycin, necessitating a repeat course of therapy.