Background: Infective endocarditis (IE) is frequently suspected but infrequently diagnosed in children. Clinicians often order echocardiograms to 'rule out' IE. In an era of cost constraint, clinically efficient strategies must be developed to eliminate unnecessary tests. We hypothesized that transthoracic echocardiography (TTE) is only useful in children in whom there is a high clinical suspicion of IE based on history, physical examination, and persistently positive blood cultures. Objective: To determine the role of TTE as a screening test for suspected IE in children. Methods: Echocardiographic reports and medical records were reviewed retrospectively for 173 consecutive patients who underwent TTE to rule out IE from January 1993 to August 1996. Results: Persistent fever was the predominant symptom leading to a suspicion of IE (120 patients [69.4%]). Fifty-seven (32.9%) of the 173 patients had congenital heart disease and 95 patients (54.9%) had indwelling venous catheters. Twenty-six patients (15.0%) were diagnosed and treated for IE. Twelve (46.2%) of these 26 patients had vegetations seen on TTE. The conditions of the remaining 14 patients were diagnosed clinically and these patients had persistently positive blood cultures. By univariate analysis, the risk factors associated with the diagnosis of IE were malaise, congestive heart failure, new or changing heart murmur, leukocytosis, hematuria, and the presence of 2 or more positive blood cultures for the same organism. The risk factors associated with positive TTE were malaise, congestive heart failure, new or changing heart murmur, leukocytosis, hematuria, and 2 or more positive blood cultures. The presence of an indwelling catheter or immunocompromised status were not predictive of vegetation or IE. Conclusions: Transthoracic echocardiography has poor sensitivity as a screening test for IE in patients with low clinical probability of the disease. A diagnostic algorithm for IE is suggested based on these data.