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We evaluated the activity of cefoperazone (CPZ) on the intestinal flora in terms of its use as a single prophylactic drug in colon surgery. Twenty-four healthy male volunteers between the ages of 20 and 40 were assigned to receive either CPZ, oral neomycin-erythromycin, or no antibiotics. A mechanical bowel preparation, Golytely, was also given to each of the subjects. With intravenous CPZ, antibiotic levels in the stool ranged from less than 2 to 649 micrograms/ml and the total fecal bacterial counts dropped 3 to 4 log10 CFU/g. Higher levels of CPZ were detected in the stools when an oral dose was added, 1,446 to 5,445 micrograms/ml, and the bacterial counts were reduced maximally 4 to 6 log10 CFU/g. The combination of the oral and intravenous doses produced suppression of the microflora and high levels in blood, all with a single antibiotic.