Cephalosporins have been recommended as prophylactic antibiotics in patients undergoing cardiovascular surgery. The major function of these antibiotics is to protect patients against Staphylococcus aureus and Staphylococcus epidermidis infections. The lowest inoculum amount responsible for infection during surgery is unknown but is probably low. To determine the comparative activities of cefazolin, cefuroxime, and cefamandole against S. aureus and S. epidermidis for prophylactic purposes, we selected five strains of S. aureus and S. epidermidis that presented homogeneous resistances to oxacillin. A continuously monitored turbidimetric method was used to evaluate cultures with variable inoculum sizes ranging from 10(6) to 1 CFU/ml and exposed to cefazolin, cefuroxime, and cefamandole at concentrations of 0.5, 1, 2, 4, 8, 16, and 32 micrograms/ml. Growth was defined as an increase of 0.1 optical density unit. The relationship between the time required for growth, the antibiotic concentration, and the initial bacterial density showed that cefamandole was more active than cefazolin, which, in turn, was revealed to be more active than cefuroxime against S. aureus and S. epidermidis.