A full-term normal neonate had acute staphylococcal endocarditis. Serial echocardiograms demonstrated abnormal echos in the region of the posterior mitral valve leaflet and aortic outflow tract that were subsequently proved to be a bacterial vegetation. This represents, we believe, the first case reported of the echocardiographic diagnosis of bacterial endocarditis in a neonate. There was progressive functional impairment of the mitral valve despite appropriate antibiotic therapy. At necropsy, a 1-cm vegetation was found attached to, and eroding through, the posterior mitral valve leaflet. The remainder of the heart, including the mitral valve apparatus, was normal. Endocarditis is a rare, but devastating, disease in a neonate, and the echocardiogram is a safe noninvasive method of making an accurate diagnosis and following the course of the disease.