Arteriovenous fistulae (AVF) between the femoral vessels were prepared in 20 rabbits to determine if local endovascular infections could be induced and if antibiotic prophylaxis could prevent infection. Twenty-four hours after bacterial challenge with 10(6) Staphylococcus aureus all 20 AVF were culture positive, whereas 19 of the 20 contralateral, unoperated femoral vessels were sterile. Two rabbits with AVF, followed for 30 days after receiving staphylocci, had intermittently positive blood cultures and had positive cultures of the AVF and heart valves at autopsy. Two groups of ten rabbits with AVF received either prophylactic oxacillin or vancomycin 0.5 h before bacterial challenge. Only 2 of 10 animals receiving oxacillin and 1 of 10 receiving vancomycin had positive AVF cultures at 24 h, a significant reduction in the incidence of endovascular infection compared with that in controls (P less than 0.001 by Fisher's exact test). This model, which reliably results in infection, can be used to study the pathophysiology, prevention, and treatment of AVF infections.