Patients treated with clindamycin were monitored for development of diarrhea and colitis in a cooperative study at three hospitals in Edmonton, Toronto, and Winnipeg, Canada. Ampicillin-treated patients were matched with dindamycin-treated patients. Diarrhea occurred in 62 (18%) of 343 clindamycin-treated patients compared with 16 (5%) of 315 ampicillin-treated patients (P < 0.001). Among the three hospitals, the rate of diarrhea associated with dindamycin therapy ranged from 10% to 23% compared with 0 to 10% for ampicillin therapy. The only identified risk factor in the development of diarrhea was increased age; clindamycin-associated diarrhea occurred in 18 (46%) of 39 patients ⩾60 years old. No correlation was observed between the risk of diarrhea and the duration of treatment, total dosage of drug, route of administration, or type of underlying disease. Pseudomembranous colitis was diagnosed in seven (2%) of 343 patients treated with dindamycin and in one (0.3%) of 315 patients treated with ampicillin.