Ultrasound contrast techniques are used widely as a screening test for intracardiac shunt. We performed a retrospective analysis of contrast echocardiograms in 29 consecutive patients with atrial septal defect (excluding Eisenmenger's) proved by cardiac catheterization. A positive (right-to-left atrial) ultrasound contrast effect was seen in 25 patients in whom catheterization pulmonary-to-systemic flow rate (Qp/Qs) was 2.2 +/- 0.9 (SD). Four patients had false-negative contrast echocardiography results; their Qp/Qs was 2.9 +/- 0.4 (p = 0.07). The percent left-to-right shunt was higher in the group with false-negative contrast echocardiographic results (65% +/- 4% vs 47% +/- 21%) (p = 0.05). Shunts with Qp/Qs < or = 2.0 had a sensitivity of 100%, whereas those with Qp/Qs > or = 2.1 had a sensitivity of 73%. In the four false-negative contrast echocardiographic results, three had findings of an atrial septal defect by pulsed Doppler, color Doppler, or both. Thus the presence of a large left-to-right shunt may decrease the sensitivity of the ultrasound contrast technique for the detection of an atrial septal defect. Contrast ultrasonography should be used in conjunction with Doppler and two-dimensional echocardiography criteria for diagnosis of atrial septal defect.