Ceftriaxone penetration into heart tissues (valves, myocardium, auricles and pericardium) and mediastinal tissues (fat and sternal bone) was evaluated after two regimens of ceftriaxone administration. Ten patients were given 1,000 g intravenously of ceftriaxone 30 min. before anesthesia. Ten other patients received the same dose and then a second 1,000 mg dose at the time of initiation of cardiopulmonary bypass. Similar and very satisfactory ceftriaxone tissue penetrations were observed in both groups. However, for some patients in the two groups and mainly in the sternal bone at the time of thorax closure, ceftriaxone levels in tissues were less than the MICs for some potential pathogens (Methicillin susceptible Staphylococcus aureus and Staphylococcus epidermidis). During the different steps of the surgical procedures all patients in both groups had tissue levels greater than the MICs for Gram negative aerobic bacilli, except for Pseudomonas spp.