Intestinal endogenous members of the family Enterobacteriaceae were eliminated in 12 human volunteers treated with 400 or 800 mg of oral norfloxacin per day for 5 days. No clones resistant to quinolone derivatives were isolated. Counts of aerotolerant streptococci were affected to various degrees, depending on their susceptibility to norfloxacin. During treatment, counts of anaerobes remained above 9.8 log10 CFU/g of feces. A total of 932 anaerobic isolates from the predominant flora (over 10(9) CFU/g) in fecal samples obtained before or during norfloxacin treatment were classified by a simple morphological and physiological scheme. The composition of this flora was fairly stable from one sample to another before treatment and was not substantially modified by norfloxacin. Intestinal resistance to colonization by exogenous microorganisms was studied in gnotobiotic mice associated with a human fecal flora. The composition of the fecal flora of the human donor and the fecal concentrations of norfloxacin in the volunteers were reproduced in the intestine of the mice. Resistance to colonization by exogenous microorganisms was reduced by norfloxacin for only 2 of 14 (14%) of the strains tested. These results suggest that norfloxacin is a good candidate for selective antimicrobial modulation of the intestinal tract in humans.