Hospitalized patients who received clindamycin or ampicillin were evaluated for gastrointestinal side effects for a period of up to six weeks after therapy was discontinued. Of 104 patients receiving clindamycin therapy, 31 (29.8%) developed diarrhea, and two (1.9%) developed pseudomembranous colitis (PMC). Of 138 patients receiving ampicillin, 24 (17.3%) developed diarrhea, and one (0.7%) developed PMC. Diarrhea persisting for three days or more was noted in 13 (12.5%) of the patients receiving clindamycin and in seven (5.1%) of those receiving ampicillin. The tendency to develop diarrhea was positively correlated with serious illness, abdominal or pelvic sepsis, and total dosage of clindamycin. Examination of stools from a patient with PMC that was associated with clindamycin therapy showed a decrease in the number of anaerobic bacteria from the numbers found in stool cultures of normal controls. Those patients who did not develop diarrhea also had fewer anaerobic bacteria and coliform organisms. Lymphocytes from the patient with PMC were hyporeactive to phytohemagglutinin and hyperreactive to clindamycin.