The coating of medical devices with antimicrobial agents has recently emerged as a potentially effective method for the prevention of device-related infections. We examined the anti-infective efficacy of intramedullary nails coated with an antiseptic combination of chlorhexidine and chloroxylenol in a rabbit model of device-related infection after fixation of an open tibial fracture. The rabbits were randomized to receive 2.8-by-100-millimeter stainless-steel tibial intramedullary nails that either were uncoated or were coated with antiseptic. After administration of anesthesia and preoperative antibiotic prophylaxis, a tibial fracture was created and then reduced with insertion of the intramedullary nail. A bacterial inoculum of 10(6) colony-forming units of Staphylococcus aureus was injected into the intramedullary canal, and the wound was sutured. Radiographs of the tibiae were made postoperatively, and the rabbits were monitored daily. They were killed at six weeks, or earlier if there was dehiscence of the wound, the fracture became grossly unstable, or the rabbit failed to thrive. The use of the antiseptic-coated nails was associated with a significantly lower rate of device-related osteomyelitis (two of twenty-two; 9 per cent) than the use of the uncoated nails (thirteen of twenty-one; 62 per cent) (p = 0.0003). The radiographic and histopathological findings were generally similar in the two groups of rabbits. Antiseptic agents were not detected in serum. The results suggest that antiseptic-coated fracture-fixation devices provide significant local protection against Staphylococcus aureus, which is the most common cause of infections related to orthopaedic devices.