Abstract Cefotetan is a new cephamycin antibiotic characterised by excellent B-lactamase stability and anti-anaerobe activity, coupled with a long half life of 3–4 h which permits twice daily dosage. A clinical trial of cefotetan in the treatment of severe oro-facial infections is presented, together with a detailed analysis of the causative organisms and their sensitivities to eight antibiotics. 50 50 patients achieved clinical cure with a treatment regime comprising cefotetan therapy and incision and drainage, with patients being transferred to oral cephradine for the final phase of therapy. Side effects were minimal and there were no instances of relapse. Significant resistance among α-haemolytic streptococci and bacteroides organisms to penicillin was observed. The streptococci were resistant due to mechanisms other than β-lactamase production. In the light of these findings and the reports of other workers it is suggested that penicillin V may no longer be the most appropriate drug for endocarditis prophylaxis, despite the most recent recommendations of the American Heart Association. Furthermore, if penicillin V is used for this purpose, a penicillin free interval of 6–8 weeks may be inadequate before this drug is used. Cefotetan is not suitable for prophylaxis against endocarditis.