A novel glycylcycline agent, tigecycline (GAR-936), was evaluated in vivo in the mouse model of peritonitis against three Enterococcus faecalis and four Enterococcus faecium isolates with different susceptibilities to vancomycin and tetracyclines, all of which were inhibited by </=0.125 micro g of tigecycline/ml. Using a single subcutaneous dose, tigecycline displayed a protective effect (50% protective dose, </=5.7 mg/kg of body weight) against all strains tested, including two with Tn925 (from the Tn916 family), which contains the Tet(M) tetracycline resistance determinant, as well as VanA and VanB strains. As expected, tetracycline and minocycline were ineffective against the isolates carrying Tn925.