Negative contrast echocardiograms of two-dimensional long axis view of the right ventricle and the atrium were compared with the results of cardiac catheterization and surgical findings in 33 adults with atrial septal defects. Contrast echocardiographic evidence of atrial communication was noted in 30 cases (91%), and, in 28 cases, the negative contrast during one cardiac cycle could be measured. This could be applied even in cases with a small left-to-right shunt or with Eisenmenger's syndrome. No obvious difference in the behavior of negative contrast was documented among the cases with distinct types of septal defects. The maximum negative contrast area and the duration of appearance in one cardiac cycle were related to the pulmonary-to-systemic flow ratio. However, a significant overlap and considerable effects of transducer angulation on measurements were documented. Thus, negative contrast echocardiography may be widely used for the noninvasive identification of a left-to-right shunt in atrial septal defects. However, the method is not appropriate for a precise quantification of three-dimensional shunt flow.