Breath-by-breath measurements of pulmonary capillary O2 transfer and ventilation were made on three subjects during and after 10 min of lower body negative pressure (LBNP) at -20, -40, and -60 torr. Loss in blood O2 stores (O2B) during and replenishment after LBNP were directly related to the intensity of LBNP. The peak rise in pulmonary capillary O2 transfer after release of LBNP was always preceded by a decrease in leg volume, indicating that O2B changes were related to blood volume shifts. The return of O2-depleted, pooled blood to the central circulation during the first minute of recovery caused significant hyperpnea. Three compartment lung model analyses from alveolar and arterial blood samples at -60 torr showed an increase in the alveolar deadspace fraction from 0.09 to 0.17, and a decline in the effective compartment from 0.83 to 0.77. The less effective lung perfusion during LBNP may explain a 30% increase in ventilation equivalent for O2.