Thirty-eight patients with enterococcal endocarditis were seen at the New York Hospital-Cornell Medical Center from 1945 through 1968. Sixteen of the 38 patients had no history of underlying heart disease. The 22 men (average age 59 years) frequently had a genitourinary source of infection. The 16 women were younger (average age 37 years) and frequently had a history of antecedent childbirth or abortion. Thirty of the 36 patients (83%) treated with penicillin (or ampicillin) and streptomycin were cured and well at least three months after cessation of therapy. Adverse reactions to antibiotic therapy developed in 15 patients. These reactions included skin rashes, toxic effect on the eighth nerve, and one fatal case of hemorrhagic enteritis. In patients who cannot receive penicillin, in vitro studies suggest that vancomycin hydrochloride plus streptomycin may be the alternative therapy of choice.