Ten cases of protracted diarrheal illness after the oral administration of lincomycin or clindamycin in standard dosages were observed in previously healthy subjects. An abrupt onset of diarrhea, crampy abdominal pain, fever, and leukocytosis was observed one to 12 days after discontinuation of the drug. Proctoscopic examination revealed erythematous friable mucosa covered with small raised, yellowish-white plaques that were sometimes confluent. Barium contrast studies of the colon demonstrated irregular shaggy mucosa, ulcerations, cobblestone appearance, and thumb printing. Rectal bipsy showed acute inflammation with pseudomembranes with focal or superficial ulcerations. All patients had a protracted course but recovered with supportive management. Follow-up barium enemas and proctoscopy were done on all patients and were normal. A history of diarrhea, fever, and mucosal changes seen on proctoscopy in a patient who has recently received one of these antibiotics should raise the possibility of colitis associated with clindamycin and lincomycin therapy.