The influence of the gentamicin dosing regimen was studied in experimental Enterococcus faecalis endocarditis. After inoculation, animals received penicillin, or penicillin plus once-daily gentamicin, or penicillin plus thrice-daily gentamicin, or no treatment. After the treatment period, bacterial densities within the vegetations (mean +/- SEM) were 6.06 +/- 0.30, 5.42 +/- 0.29, 4.98 +/- 0.10 and 9.97 +/- 0.16 log cfu/g for the four groups. All regimens produced significant reductions in bacterial density when compared with controls; penicillin plus thrice-daily gentamicin resulted in a significant difference from penicillin alone. Although once-daily regimens have proved effective in trials involving other organisms, such regimens do not appear to be so optimal for the treatment of enterococcal endocarditis.