We have evaluated the benefits of low versus high doses of gentamicin combined with procaine penicillin (1.2 X 10(6) U three times daily) in the treatment of streptomycin-resistant experimental enterococcal endocarditis in rabbits. The mean peak serum gentamicin concentration in animals treated with low-dose gentamicin (0.75 mg/kg three times daily) was 3.06 micrograms/ml (range, 2.1 to 4.2 micrograms/ml), and it was 8.05 micrograms/ml (range, 4.5 to 16.1 micrograms/ml) in animals treated with high-dose gentamicin (2 mg/kg three times daily). The mean log10 colony-forming units of enterococci per gram of cardiac valve vegetation in animals treated with procaine penicillin combined with low- or high-dose gentamicin were 2.4 +/- 1.2 and 1.4 +/- 1.3, respectively (P = not significant) after 3 days of treatment and 1.7 +/- 1.2 and 1.7 +/- 1.5, respectively (P = not significant), after 5 days of therapy. The median peak serum bactericidal titer was 1:8 in animals treated with low- or high-dose gentamicin. We detected no significant difference between low- or high-dose gentamicin combined with procaine penicillin in the efficacy of treatment of streptomycin-resistant experimental enterococcal endocarditis.