The utility of combined peripheral vein contrast 2-dimensional echocardiography (2-D echo) and radionuclide shunt detection was evaluated in 25 patients with suspected atrial septal defect (ASD) in whom the diagnosis was confirmed at cardiac catheterization: 14 patients had ASD and 11 had no intracardiac shunt. Contrast 2-D echo correctly diagnosed 13 of 14 patients with ASD, but there were 2 false-positive diagnoses in the 11 patients without ASD. Radionuclide shunt studies correctly identified all 14 patients with ASD, but yielded 5 false-positives results among the 11 without ASD. After altering the radionuclide processing technique, there were only 2 of 11 false-positive shunt studies, and the correlation of radionuclide shunt magnitude with cardiac catheterization improved (r = 0.49, p less than 0.025 to r = 0.75, p less than 0.001). Thus, the improved processing method improved both the qualitative and quantitative accuracy of radionuclide shunt detection. The combination of contrast 2-D echo and radionuclide shunt detection led to a proper diagnostic and therapeutic decision in 24 of 25 patients. Therefore, these combined modalities are clinically useful in the evaluation of patients with suspected ASD.