The effect of warfarin treatment on an experimental Staphylococcus epidermidis endocarditis was studied. Warfarin was found to affect both the induction and course of the infection of catheter-induced endocardial vegetations. In warfarin-treated rabbits, larger bacterial inocula were needed to induce an infection, and the degree of infection of the vegetations was also significantly lower, eventually resulting in the total elimination of the bacteria from the vegetations. Thus, warfarin treatment seems to have an inhibitory effect on the induction and development of an S. epidermidis infection of the endocardium. The results differ from previous findings in studies done with Streptococcus anguis, where warfarin was found to have no effect on the induction or course of the infection of endocardial vegetations, which suggests that different mechanisms are involved in the pathogenesis of endocarditis caused by these two species of bacteria.