In the treatment of subacute bacterial endocarditis with penicillin1 four organisms were encountered which were highly or completely resistant to penicillin. One of these, Hemophilus parainfluenzae, was encountered before streptomycin was available. Negative cultures of blood could not be obtained after many weeks of penicillin therapy in daily dosage up to 2,000,000 units. The organism was not inhibited in vitro by any concentration of penicillin which it was possible to obtain in vivo. It was inhibited in vitro by therapeutic concentrations of sulfamerazine, yet negative cultures of blood could not be obtained by the use of sulfamerazine therapy alone. Cure resulted from the combined administration of penicillin in daily dosage of 500,000 to 1,000,000 units and sulfamerazine in dosage to give a level in the blood of 0.8 to 11 mg. per cubic centimeter. The patient, a boy of 8, is alive and engaged in normal activity at school