The diagnosis of pediatric infective endocarditis (IE) is often difficult. Strict diagnostic criteria were developed in 1981 by von Reyn and in 1994 at Duke University and have been evaluated thoroughly in adults. Both criteria consider microbiologic data, physical exam findings, and predisposing cardiac disease. The most striking differences are that the Duke Criteria (DC) allow use of pathologic or clinical features for definite IE and consider echocardiographic findings, whereas the von Reyn Criteria (VRC) require pathologic evidence to diagnose definite IE. Several adult IE series have demonstrated increased sensitivity of the DC compared to VRC. No North American series has evaluated these criteria for diagnosis of pediatric IE. We compared the DC to the VRC in 69 children identified by hospital discharge diagnosis who were treated for IE at two large pediatric centers from 1978 through 1990. All were evaluated echocardiographically. 60/69 patients had predisposing heart disease, most congenital. By VRC, 12/69 (17%) were definite IE, 22/69 (32%) were probable IE, 27/69 (39%) were possible IE, and 8/69 (12%) were rejected. By DC, 47/69 (68%) met criteria for definite IE, 22/69 (32%) were possible and none were rejected. All 22 cases classified as probable by VRC were definite by DC. Of cases rejected by VRC, 4/8 were definite and 4/8 were possible by DC. The 12 definite cases classified by VRC (i.e. with pathologic confirmation) were re-classified using clinical criteria only: 8 became probable, one possible, and 3 were rejected by VRC; 9/12 remained definite and 3 were re-classified as possible by DC. Among 44/47 definite cases by clinical DC (excluding 3 confirmed pathologically), 30/44 are probable, 12/44 are possible, and 2/44 are rejected by VRC when echocardiographic data are ignored. We conclude that application of DC to pediatric patients with suspected IE identifies many more patients with definite IE and rejects fewer patients than VRC and that echocardiographic findings add greatly to the increased sensitivity of DC.