The experience of this laboratory with the treatment of Clostridium-induced colitis in experimental animals and in patients was reviewed. Optimal results in hamsters were achieved with the antibiotics vancomycin, metronidazole, and tetracycline. Cholestyramine was less effective. The outcome for animals given corticosteroids and Clostridium sordellii antitoxin systemically was not different from that for untreated control animals. The second facet of the study was a retrospective review of therapy in 272 patients with C. difficile-induced diarrhea or colitis. No specific therapy was given to 56 patients who had mild symptoms or were improving at the time the toxin was detected. The therapy most frequently used was oral vancomycin, which was given to 189 patients, including 100 with confirmed pseudomembranous colitis. The response rate was 97%, but 46 patients (24%) relapsed when treatment was discontinued. Response to cholestyramine was favorable in 12 of 19 patients. The results with metronidazole and bacitracin were uniformly good, although the experience was limited.