Vancomycin-resistant enterococci have become important nosocomial pathogens in many institutions. The gastrointestinal tract of susceptible hosts serves as the likely reservoir from which the organism is disseminated. To study factors promoting colonization and the efficacy of decontamination therapy with antimicrobial agents, a model of gastrointestinal colonization with vancomycin-resistant Enterococcus faecium was developed in CF1 mice. At baseline, all animals were colonized with non-vancomycin-resistant enterococci (5.0 log10 CFU/g), but vancomycin-resistant organisms were not detectable. Following gastric inoculation with 5 x 10(8) CFU of a clinical isolate of vancomycin-resistant E. faecium, the strain transiently colonized the gastrointestinal tract of 100% of mice but was undetectable by Day 14 (< or = 2.7 log10 mean CFU/g). In animals who received 5 mg of streptomycin per ml or 250 micrograms of vancomycin per ml in drinking water, colonization with the organism occurred at significantly higher bacterial counts than in controls at 7 days following inoculation (9.4 for vancomycin, 9.2 for streptomycin, and 5.1 log10 mean CFU/g for controls; P < 0.05). Fecal concentrations of vancomycin-resistant E. faecium persisted at high counts through Day 22 in mice receiving these antibiotics, but low counts were also still detected in 3 of 10 control animals. In mice with previously established vancomycin-resistant E. faecium colonization, oral administration of ramoplanin, a lipoglycodepsipeptide to which the strain was susceptible, suppressed growth of all enterococci in feces, including the vancomycin-resistant strain after 7 days of therapy (< or = 3.1 and < or = 3.3 log10 mean CFU/g for vancomycin and streptomycin groups, respectively). All mice had a recurrence of colonization with vancomycin-resistant E. faecium after the ramoplanin was discontinued. In summary, this animal model demonstrates the importance of antibiotics in predisposing to gastrointestinal colonization with vancomycin-resistant Enterococcus spp. Although treatment with ramoplanin temporarily suppressed the organism, recurrence of colonization due to relapse or reinfection occurred.