Pharmacologic data are presented on 39 children treated for osteomyelitis with one of the following antibiotics: methicillin, dicloxacillin, cephaloridine, or cefazolin. The concentrations of drug in pus and bone were correlated with serum concentrations, with the susceptibilities of Staphylococcus aureus strains isolated from the patients, and with the degree of drug protein-binding. The penetration of the antibiotics into pus and bone was similar for the two penicillins and for the two cephalosporins despite the disparate protein-binding affinities of these drugs. The agents attained concentrations in tissues that were at least several fold, and often more than tenfold, greater than the MIC and MBC values of the S. aureus stains. These data provide a basis for selection of antimicrobial agents for treatment of osteomyelitis.