Use of broad-spectrum antibiotics is known to cause changes in the intestinal microflora of man. The present study was initiated to determine the effect of oral fosfomycin calcium on several groups of microorganisms indigenous to the gut. Data from this double-blind study indicate that 2 g of fosfomycin given daily in four divided doses for 28 days increased the incidence of soft stools. No significant changes in numbers of staphylococci or Candida were observed during treatment. Although there was no significant change in total coliforms, the numbers of E. coli decreased markedly from 10(5) to 10(2) organisms/g feces. Concurrent with this decrease, the Klebsiella-Enterobacter counts increased from 10(3) to 10(6) organisms/g feces. Two weeks posttreatment the E. coli and the Klebsiella-Enterobacter counts approached pretreatment levels. These observations are similar to those reported for ampicillin. During the course of treatment when the E. coli dropped precipitously the few surviving E. coli still were suceptible to fosfomycin as determined by an agar diffusion disc test.