The efficacy of telavancin, a novel lipoglycopeptide, was evaluated in experimental endocarditis in rabbits using two clinical isolates of glycopeptide-intermediate Staphylococcus aureus: ATCC 700788 and HIP 5836. Infected rabbits were treated for 2 days with telavancin (10 mg/kg of body weight once daily intravenously) or vancomycin (1 g twice daily intravenously), administered with a computer-controlled infusion pump system simulating human serum kinetics. Vegetations were harvested at 16 h postinoculation in the control group and at the end of treatment in the drug-treated group. For ATCC 700788, MICs and minimal bactericidal concentrations (MBCs), respectively, were 1 mg/liter and 4 mg/liter for telavancin and 8 mg/liter and 128 mg/liter for vancomycin. For HIP 5836, MICs and MBCs, respectively, were 4 mg/liter and 8 mg/liter for telavancin and 8 mg/liter and 128 mg/liter for vancomycin. Peak and trough levels were 90 g/ml and 6 g/ml, respectively, for telavancin and 46 g/ml and 6 g/ml, respectively, for vancomycin.