Animal models of endocarditis have helped understanding of the mode of action of antibiotics in prophylaxis. During bacteraemia, some microorganisms will adhere to damaged cardiac valves. The proportion of bacteria that will adhere depends largely on intrinsic properties of the strain. In the absence of antibiotics, the microorganisms will either be eliminated by local host defence mechanisms if the inoculum is low enough or will begin to grow approximately 2 h after the development of bacteraemia and endocarditis. In the presence of antibiotics, the growth of adherent bacteria is inhibited and local host defences have longer to eliminate the bacteria. In cases where the number of adherent bacteria is relatively low, a short period in inhibitory antibiotic activity (6 hours) is sufficient to eliminate the bacteria and lead to successful prophylaxis. If the number of bacteria is high, a longer duration of the inhibitory effect is necessary. These experimental data provide a rationale for practical recommendations for the prophylaxis of endocarditis in humans.