Twenty-eight patients who underwent open-heart surgery were divided into three groups, each of which received a different antibiotic from the cephalosporin series (cephalotin, cefazolin or cefamandole) in order to prevent infection. All antibiotics were given via intravenous infusion in a dosage of 2 g prior to surgery. To clarify the question of antibacterial activity under operative conditions with the cardiopulmonary bypass, the serum and tissue levels were determined before, during and after the surgical procedure. The effectiveness of the cephalosporins against bacteria most frequently encountered in open-heart surgery was demonstrated and substantiated by the serum and tissue concentrations. It became apparent that, in view of the favorable serum and tissue levels during and after the cardiopulmonary bypass, cefamandole should be considered the antibiotic of choice in preventing infections during open-heart surgery.