Experiments were designed to study the natural history of infection in different parts of the vascular system. Sterile vegetations were produced in rabbits by placing catheters in the inferior vena cava, tricuspid or aortic valves, and thoracic or abdominal aorta and then were infected by the intravenous inoculation of Streptococcus sanguis. At 1 day after bacterial challenge, all VEGS were infected, mean bacterial densities being highest in the VEGS of the aortic and tricuspid valves. By 14 days, there was a significant decrease in the mean bacterial density in all VEGS except for the aortic valve: the VEGS of the inferior vena cava and abdominal aorta were sterile, as were half of those of the thoracic aorta. There were no deaths except for animals with aortic valve infection. Dexamethasone inhibited the sterilization of the thoracic aorta VEGS, but was without effect on aortic valve VEGS, 5 mm distant. Sterilization of tricuspid valve VEGS after catheter removal was also inhibited by dexamethasone. Thus, there are host defense mechanisms which lead to the sterilization of infections everywhere in the vascular system except in the left side of the heart, and these mechanisms, as yet undefined, are inhibited by dexamethasone.