A single intravenous 2 g dose of cefoxitin, a broad spectrum antibiotic, was administered prophylactically just prior to operation on 60 patients undergoing total joint replacement (30 total hip replacements, 30 total knee replacements). Specimens of blood, bone, and synovial fluid were obtained during the operative procedure and assayed for cefoxitin concentration. Peak serum levels drawn five minutes after completion of antibiotic administration showed an average of 191 mcg/ml. Synovial fluid specimens were obtained an average of 33 minutes following antibiotic administration with a mean cefoxitin concentration of 72 mcg/ml. Bone samples from either the femoral condyle or femur head were taken an average of 65 minutes after the antibiotic was given and showed a mean cefoxitin concentration of 12 mcg/g. Simultaneous serum concentration was 63 mcg/ml. No allergic reactions occurred despite a history of skin rash after penicillin in eight patients. One patient developed deep infection caused by poor healing of the skin over the surgical site, thus leading to infection and involvement of the joint well after prophylaxis ended.