The results of studies performed with animal models of experimental infective endocarditis have provided valuable information about the pathophysiology, natural history, and treatment of this infection. The Freedman rabbit model of experimental infective endocarditis is relatively simple to perform, is reproducible, and with minor modifications has become the standard model for the study of experimental endocarditis. The following are the major advantages of the Freedman model: (1) its relatively low cost and simplicity permit the study of large numbers of animals required for statistical analysis of results; (2) the model enables accurate control of the timing of the onset of infection, the administration of antimicrobial agents, and the duration of infection and treatment before the animal is killed; and (3) the experimental infection in rabbits histologically resembles the pathologic changes that occur in this infection in humans. This model has some disadvantages: (1) the artificially induced trauma to rabbit cardiac valves is different pathophysiologically from the conditions that predispose humans to infective endocarditis; (2) a larger inoculum of bacteria is required to produce infections in rabbits than that which causes human endocarditis; and (3) the rabbit model is a more severe, acute form of infection than human infective endocarditis, and survival of untreated animals for longer than 2 weeks is unusual. One should exercise considerable caution in extrapolating the results obtained from animal experimental infective endocarditis to human infection.