Several patients hospitalized in our 12-bed medical ICU were found to haveClostridium difficileassociated colitis. Stool cultures of all patients identified eight cases (three culture positive, and five culture and cytotoxin positive), seven of which were geographically and temporarily clustered within a 2-wk period. At least one patient appeared to contract the disease after hospitalization and in the absence of antibiotic therapy or other known major risk factors. The outbreak highlights the problem ofC. difficilein the ICU. We believe that a heightened awareness of the multiple risk factors and preventive measures, along with consideration of possible nosocomial transmission, will be necessary to prevent or arrest future clusters of cases in the ICU. The diagnosis of one patient with this infection in a unit should prompt a review of all other patients within the unit.