To evaluate the effects of parenteral cefoperazone therapy upon human fecal flora, fecal specimens obtained from four patients before and during therapy (as well as after therapy for one patient) were cultured quantitatively for facultative, aerobic, and anaerobic bacteria and for fungi. Cefoperazone therapy was associated with major changes in fecal flora. There was suppression to undetectable levels or an appreciable reduction in all anaerobic bacteria as well as suppression of all initially detected Enterobacteriaceae. During therapy, there was acquisition or an increase in counts of Candida spp., so that these became the most numerous fecal microorganisms in all patients. In addition, Pseudomonas spp. and coagulase-negative Staphylococcus sp. were acquired by three patients. These marked alterations in flora have potentially important consequences.