Thirty-two patients with acne completed a randomized, double-blind study using topical 1% clindamycin phosphate or its vehicle applied twice daily for 8 weeks for a study of its effects on the intestinal microflora. Two clindamycin patients and one vehicle patient had Clostridium difficile in stools prior to therapy. Of the remaining twenty-nine patients, four of nineteen patients who used clindamycin and none of ten patients who used vehicle had C. difficile detected during treatment; the difference was not statistically significant. There was no diarrhea in the clindamycin group, even though clostridial cytotoxin was found transiently in two patients. Self-limited diarrhea occurred in one vehicle-treated patient, whose stool culture was negative but whose stool specimen showed a positive reaction for C. difficile cytotoxin. With the use of a bioassay, clindamycin was not detected in urine or stool of any patient. No significant changes in Bacteroides fragilis counts in stools were observed in either group.