Sixty eight patients received either an oral single dose of 300 mg (or 300 mg/12 h), or an oral single dose of 600 mg (or 600 mg/24 h) of rifampicin. In every case samples of serum and bone were collected 3 h, 12 h, and 24 h after the last oral dose. Rifampicin levels measured at 3 h and 12 h in cortical bone samples increased significantly with the dose of the drug. The only dose which determines activity in cortical bone at the 3rd hour was the dose of 600 mg. When the dose was increased from 300 mg/12 h to 600 mg/24 h the ratio spongious bone/serum increased from 0.19 to 0.41 at 3d h and from 0.24 to 0.29 at the 12th hour; the ratio cortical bone serum was 0.20 at the 3rd hour after a dose of 600 mg. In any case tissue levels varied in a parallel direction to serum levels and were superior in spongious bone to the MIC of S. aureus sensitive strains until 12 h after the 600 mg dose. According to these results, it appears that the best dose for treating S. aureus bone infection seems to be 600 mg/12 h.