BACKGROUND Streptococcus viridans continues to be the most frequent causal agent of infective endocarditis. Treatment has become more complicated due to the increase in resistance to penicillin and cephalosporins. In order to study the possible efficacy of vancomycin, this antibiotic was investigated in rabbits as a monotherapy and in association with gentamicin. The effects were compared with a control group and a group given classical penicillin-gentamicin treatment. METHODS Minimum inhibitory concentration, minimum bactericidal concentration, lethality curves and synergism were determined against Streptococcus sanguis II. Infective endocarditis was induced in 80 rabbits, which were infected via catheter. Treatment was started 48 hours after infection, and lasted 5 days. The animals were divided into 4 groups of 20 rabbits each: 1, untreated controls; 2, penicillin-gentamicin; 3, vancomycin; 4, vancomycin-gentamicin. Response to therapy was evaluated with mortality curves, negativization of blood cultures, concentration of Streptococcus sanguis II in aortic vegetations, rate of sterilization of vegetations, body weight and serum bactericidal capacity. RESULTS Vegetations weight was significantly lower in treated groups than in controls; lower weights were found in groups 2 and 4. The lowest vegetation weight was recorded in group 4, the only treatment that sterilized 75% of vegetations. Death occurred only in the control group (10%). Negativization of blood cultures was greatest and most rapid in group 4. Serum bactericidal capacity was greater after the two combined treatments, and highest in group 4. CONCLUSIONS Combined treatment with vancomycin-gentamicin may be highly efficacious in patients with endocarditis caused by penicillin-resistant Streptococcus viridans.