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Although the inspiratory ‘collapse’ of the inferior vena cava (IVC) has been used to signify normal central venous pressure, the effect of the manner of breathing IVC size is incompletely understood. As intra-abdominal pressure rises during descent of the diaphragm, we hypothesized that inspiration through diaphragmatic excursion may have a compressive effect on the IVC.We measured minimal and maximal intrahepatic IVC diameter on echocardiography and popliteal venous return by spectral Doppler during isovolemic inspiratory efforts in 19 healthy non-obese volunteers who were instructed to inhale using either diaphragmatic or chest wall expansion. During inspiration, the maximal diaphragmatic excursion and popliteal vein flow were compared between breathing methods. The IVC ‘collapsibility index,’ IVCCI, was calculated as (IVCmax−IVCmin)/IVCmax. The difference in diaphragmatic excursion between diaphragmatic and chest wall breaths in each subject was correlated with the corresponding change in IVCCI. Diaphragmatic breathing resulted in more diaphragmatic excursion than chest wall breathing (median 3.4 cm, range 1.7–5.8 vs. 2.2 cm, range 1.0–5.2, P= 0.0003), and was universally associated with decreased popliteal venous return (19/19 vs. 9/19 subjects, P< 0.004). The difference in diaphragmatic excursion correlated with the difference in IVCCI (Spearman's rho = 0.53, P= 0.024).During inspiration of equivalent tidal volumes, the reduction in IVC diameter and lower extremity venous return was related to diaphragmatic excursion, suggesting that the IVC may be compressed through descent of the diaphragm.