An association of pefloxacin plus fosfomycin was used as antibioprophylaxis in beta lactam allergic patients who underwent cardiac surgery with cardiovascular-bypass. Pefloxacin (800 mg), was administered orally, one hour before anesthetic induction and fosfomycin (60 mg/kg) was injected at the time of induction. The whole course of prophylaxis wat 24 hours. Antibiotic concentrations were measured in serum before (P1, P2) during (C1, C2, C3, C4) and after cardiovascular-bypass (P3) and in bone, endocardiac and pleural tissues. The efficacy was evaluated on clinical and biological data. Antibiotic levels of pefloxacin were measured by HPLC and those of fosfomycin by bacteriological method. Antibiotic concentrations are high in blood and tissues, without evidence of cardiovascular-bypass influence. The tissue penetration of both drugs is excellent. Two patients have presented serious post-operative infections. The pharmacokinetic of pefloxacin associated with fosfomycin is appropriate during cardiovascular-bypass and the local antibiotic concentrations are above the MIC of the strains commonly responsible of post operative infections in cardiovascular surgery. The clinical efficacy of this prophylaxis must be studied in a large population of patients.