Short-term administration of rifampin was evaluated as a means of preventing or eradicating infection due to foreign bodies. Tissue cages were implanted into guinea pigs and subsequently infected with 10(3) colony-forming units of Staphylococcus aureus Wood 46. Infection developed in all tissue cages. Rifampin was administered thereafter intraperitoneally at a dosage of 7.5 mg/kg every 12 hr for 48 hr, and the tissue-cage fluid was monitored for possible development of infection by quantitative bacteriologic methods for 15 days. In all cases rifampin prevented or eradicated tissue-cage infection if treatment was initiated either 3 hr before or less than or equal to 12 hr after inoculation of microorganisms but was ineffective if initiated greater than 12 hr after inoculation. In cases of failure of treatment, rifampin-resistant variants could be demonstrated. Rifampin seems to prevent or eradicate tissue-cage infection only if given early after bacterial inoculation.