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Cross-sectional echocardiographic visualization of the interatrial septum in both normal persons and patients with atrial septal defects has been reported. Although septal defects can generally be visualized, false positives are frequently encountered. This study evaluated whether visualizing the patterns of contrast flow in the region of an apparent atrial septal defect by cross-sectional echocardiography could aid in the differentiation of true defects from false positives. We studied 25 patients 13 with intact interatrial septa and 12 with atrial septal defects. Contrast was visualized in the right atrium in 24 of 25 patients (all 13 normal patients and 11 of 12 patients with atrial septal defects). In all patients with intact interatrial septum, the peripherally injected contrast material homogenously filled the right atrium, delineating the position and integrity of the interatrial septum. In two of 11 patients with atrial septal defects, evidence of right-to-left shunting through the defect confirmed its presence. In the remaining nine patients, the flow of blood from left atrium to right atrium, following the path of the left-to-right shunt, produced an echo-free area along the right margin of the interatrial septum, or an area of negative contrast. This phenomenon was produced by the non-contrastcontaining blood flowing through the septum and displacing the contrast-containing blood from along the righthand portion of the septum. This study suggests that peripheral injection of echocardiographic contrast material may be of value in detecting atrial septal defects in patients with predominant left-to-right shunting when contrast flows are evaluated using cross-sectional echocardiography.