Cloxacillin diffusion into spongious and cortical bone was studied in 20 patients undergoing total replacement of the hip, after an oral single-dose of 1 g (10 patients) or an oral dose of 1 g every 8 hours (10 patients). Serum and bone samples were collected 2 and 3 hours after the last dose and assayed for antibiotic concentration by a microbiological method. Bone levels were similar in any group of patients, but significantly higher in spongious bone than in cortical bone. The bone/serum concentration ratios were 0.15 for spongious bone and 0.10 for cortical bone. Calculations from these data showed that adequate local levels inhibitory to Staphylococcus aureus, would be achieved by cloxacillin administration of 1 g dose every 4 hours orally.