To investigate whether atrial septal defect (ASD) modifies the left ventricular (LV) hemodynamic response to a fall of intrathoracic pressure (Mueller maneuver), we studied 15 patients with an uncomplicated ASD and 16 healthy control subjects. LV function was measured by M-mode and Doppler echocardiography at rest and during the maneuver. Indicator-dilution technique was used to quantify the pulmonary-to-systemic flow ratio. During comparable changes (means +/- SE) of intrathoracic pressure (-33 +/- 2 mmHg in persons with ASD vs. -34 +/- 2 mmHg in those without), LV systolic function and filling diminished in both groups but patients with ASD showed smaller reductions in LV stroke dimension (-0.9 +/- 0.5 vs. -2.5 +/- 0.4 mm; P = 0.016), peak diameter shortening rate (-4 +/- 2 vs. -12 +/- 2 mm/s; P = 0.007), transmitral velocity-time integral (-1.0 +/- 0.3 vs. -2.2 +/- 0.4 cm; P = 0.022), and cardiac output (-6 +/- 3 vs. -18 +/- 3%; P = 0.029). The pulmonary-to-systemic flow ratio increased from 2.1 +/- 0.1 to 2.6 +/- 0.2 in the ASD group (P = 0.014). In conclusion, LV function diminishes significantly in healthy persons during the Mueller maneuver. In patients with ASD, the changes are directionally similar but quantitatively smaller. An interatrial communication mitigates the impairment of LV function after an acute and sustained drop of intrathoracic pressure.