Rifaximin is a poorly absorbed rifamycin antimicrobial drug with in vitro activity against Gram-positive, Gram-negative and anaerobic bacteria. The minimal concentration that inhibits 90% of strains of bacterial pathogens (MIC90) ranges between 32 and 64 microg/ml. Less than 1% of the drug is absorbed after oral administration. After three days of therapy, the average fecal level of this drug is 8000 microg/g of stool. Selection of resistant mutants, a problem with the related rifampin, appears to be unusual with rifaximin. Rifaximin shortens the duration of travelers' diarrhea and non-dysenteric diarrheal illness due to enterotoxigenic, enteroaggregative E. coli and Shigella sonnei without major alteration of aerobic fecal flora and without important side effects. The drug has been successfully used in preliminary studies of small bowel bacterial overgrowth syndrome and hepatic encephalopathy. To explain the beneficial effect of the drug on bacterial diarrhea without change in colonic flora or high rates of pathogen eradication, rifaximin may be more active against pathogens in the small bowel rather than the colon and/or the drug may alter the virulence of enteric pathogens in addition to organism inhibition.