A cardiac murmur is a very common finding in the first few days of life. It is traditionally believed that lesions creating left-to-right shunts do not present so early. This study was aimed to define and to classify the causes of a murmur in a newborn with an otherwise normal examination. All echocardiograms performed on newborns aged 1-5 days who were referred for evaluation of a murmur in a 3-year period were reviewed. Newborns with additional clinical signs or antenatal diagnosis of a cardiac disease were excluded. Of 20,323 live births, there were 170 newborns referred for echocardiogram solely because of a murmur. Of these, 147 (86%) were found to have structural heart defects. The most common lesions found were those creating left-to-right shunts (66%). Ventricular septal defect was the most common single lesion (54/147, 37%), followed by patent ductus arteriosus (34 newborns, 23%). The combination of both was found in 10 newborns (7%). Six newborns (4%) had pulmonary valve stenosis and three (2%) aortic valve stenosis. Seven newborns (5%) had unforeseen complex heart disease. For five of them, delayed diagnosis would have resulted in potentially life-threatening conditions. There was no correlation between the category of lesion and the age of presentation. The audible threshold of a murmur correlated with a maximum instantaneous gradient of 25 mm Hg (range 11-46 mm Hg). Thirteen percent of newborns with isolated heart murmur had no identifiable structural heart disease. These data suggest that most asymptomatic newborns presenting with a murmur in the first days of life have structural heart disease. Some of the more serious defects would not have been diagnosed without early echocardiography. A left-to-right shunt, particularly a ventricular septal defect, may cause a murmur even the first day of life and is probably more common that has been acknowledged.