To determine the efficacy of antibiotic catheter lock solution in preventing catheter-related infections, silicone catheters were tunneled and inserted into the jugular veins of 18 rabbits. The catheters were challenged with an intraluminal injection of 10(5) CFU of slime-producing Staphylococcus epidermidis in 0.1 ml of water. The catheters were maintained on heparin (100 IU/ml) flush for the first 3 days. On day 3, quantitative blood samples for culture were obtained from the catheters and ear veins, which documented catheter-related bacteremia, and the rabbits were randomized to have their catheters flushed as follows: five animals were continued on heparin (100 IU/ml), five animals received vancomycin (3 mg/ml) with heparin (100 IU/ml), and eight animals received 3 mg of minocycline per ml with 30 mg of EDTA per ml (M-EDTA). All animals were killed at day 7. Blood, catheters, jugular veins, and heart valves were cultured quantitatively. Animals maintained on heparin developed catheter-related colonization, bacteremia, septic phlebitis, and endocarditis. Vancomycin-heparin partially prevented catheter colonization, bacteremia, and phlebitis (P = 0.2). M-EDTA completely prevented catheter colonization, catheter-related bacteremia, and phlebitis in all of the animals (P < 0.01). Tricuspid endocarditis was equally prevented by vancomycin-heparin and M-EDTA (P < or = 0.06). In conclusion, the M-EDTA catheter flush solution was highly efficacious in preventing catheter-related colonization, bacteremia, septic phlebitis, and endocarditis in rabbits.