• One hundred seven patients with cystic fibrosis (CF) and 54 other patients with risk factors for Clostridium difficile–associated disease were entered into a bacteriologic study to compare the rate of recovery of C difficile and cytotoxin in feces with occurrence of diarrhea and to investigate potentially protective or permissive relationships of fecal flora. Toxigenic C difficile was recovered from 22% of CF patients and 11% of patients with other diagnoses. Unlike the latter group, the majority (12/15) of CF patients who had cytotoxin recovered had formed stools and no history of diarrhea. Explanations for the lack of symptoms are speculative. Stool flora of CF patients was significantly more likely to include several bacteria with known inhibitory effects on C difficile. Recovery of C difficile and cytotoxin, however, was not associated with the decrease in rate of recovery or the mean bacterial count of any bacterium of fecal flora.