The model of plastic-catheter induced left-sided enterococcal endocarditis has been used since 1970 in rabbits and since 1978 in rats in order to describe the pathophysiology of this unique infectious disease and to assess the most efficacious antibiotic regimens for treatment and prevention. A critical review of the experimental design is presented with a proposal of longer duration of therapy, recognition of relapse, and reisolation of infecting strains for susceptibility testing. The natural history of left-sided experimental enterococcal endocarditis is described and the results of classical beta-lactam-aminoglycoside combinations are reviewed. Interesting new observations on antibiotic dosing principles are discussed and new combinations of antibiotics against beta-lactamase producing enterococcal strains, strains highly resistant to gentamicin or resistant to glycopeptide antibiotics, are appraised for treatment and prophylaxis.