Studies to date have indicated that nutritionally-variant streptococci (NVS) causing bacterial endocarditis are frequently inhibited but not killed by low concentrations of penicillin. We report a patient with endocarditis due to a NVS strain which was killed in vitro by penicillin at a concentration of 0.09 microgram/ml. Despite therapy with intravenous penicillin for four weeks, the infection relapsed and was then cured by combined penicillin-gentamicin in therapy. In vitro studies demonstrated a synergistic effect of these two antibiotics. This experience suggests that combination therapy with penicillin and an aminoglycoside may be required for cure of all cases of nutritionally-variant streptococcal endocarditis regardless of in vitro susceptibility to penicillin.