The development of rifaximin- and rifampicin-resistant intestinal coliforms was studied in 27 subjects receiving rifaximin for 3 days by plating stool samples on media containing rifaximin 200 mg/L or rifampicin 64 mg/L before treatment (day 0), after treatment was completed (day 3), and after a further 2 days (day 5). The susceptibility of enterococci grown on day 0 and day 3 was also studied in 71 subjects. Significant increases in antimicrobial-resistant coliform flora were not seen in either the rifaximin-treated or the placebo-treated subjects. Enterococci recovered pre- and post-treatment showed similar susceptibilities. Rifaximin did not select for significant resistance in the Gram-negative and Gram-positive intestinal flora during therapy.