We followed up 112 patients in the University of Washington Burn Center, Seattle, for the development of Clostridium difficile diarrhea. Diarrhea developed in 20 patients with a mean burn size of 42%, mean age of 38 years, and 49 mean total antibiotic days, for an incidence of 17%. Eleven patients had 16 episodes of nonspecific diarrhea. Nine patients had 11 episodes of C difficile-positive diarrhea and 15 episodes of nonspecific diarrhea for an incidence of 45% of all patients with diarrhea. There were no differences in patient age, burn size, or length of stay between the groups. When the 31 episodes of nonspecific diarrhea were compared with the 11 episodes of C difficile diarrhea, there were no differences between the groups in temperature, albumin levels, or total number of antibiotic days preceding the episodes of diarrhea. The only significant finding that differed between the two types of diarrhea was the white blood cell count on the day of diagnosis. The nonspecific diarrhea was self-limited, requiring antimotility agents in 45% of the episodes. The C difficile diarrhea responded promptly to vancomycin hydrochloride, with resolution of symptoms in an average of 3.3 days. There were two recurrences, and both responded to a second course of vancomycin.