The purpose of this study was to determine the effect of acute increases in pulmonary vascular pressures, caused by the application of lower-body positive pressure (LBPP), on exercise alveolar to arterial PO₂ difference (A-aDO₂), anatomic intra-pulmonary (I-P) shunt recruitment and ventilation. Eight healthy males performed graded upright cycling to 90% VO_2max under normal conditions and with 52 mmHg (1 psi) of LBPP. Pulmonary arterial (PAP), and pulmonary artery wedge pressures (PAWP) were measured with a Swan-Ganz catheter. Arterial blood samples were obtained from a radial artery catheter, cardiac output (Q) was calculated by the direct Fick method, and anatomic I-P shunt was determined by administering agitated saline during continuous 2-D echocardiography. LBPP increased both PAP and PAWP while upright at rest, and at all points during exercise (mean increase in PAP and PAWP 3.7 and 4.0 mmHg respectively, p<0.05). There were no differences in exercise VO₂ or Q between control and LBPP. Despite the increased PAP and PAWP with LBPP, A-aDO₂ was not affected. In the upright resting position, there was no evidence of shunt in the control condition, whereas LBPP caused shunt in one subject. At the lowest exercise workload (75W) shunt occurred in 3 subjects during control and in 4 subjects with LBPP. LBPP did not affect I-P shunt recruitment during subsequent higher workloads. Minute ventilation and arterial PCO₂ were not consistently affected by LBPP. Therefore, small acute increases in pulmonary vascular pressures from LBPP do not widen exercise A-aDO₂, nor consistently affect I-P shunt recruitment or ventilation.