Based on previous water immersion results, we tested the hypothesis that the acute 0-G-induced increase in cardiac output (CO) is primarily caused by redistribution of blood from the vasculature above the legs to the cardiopulmonary circulation. In seated subjects (n = 8), 20 s of 0 G induced by parabolic flight increased CO by 1.7 ± 0.4 l/min (P <0.001). This increase was diminished to 0.8 ± 0.4 l/min (P = 0.028), when venous return from the legs was prevented by bilateral venous thigh-cuff inflation (CI) of 60 mmHg. Because the increase in stroke volume during 0 G was unaffected by CI, the lesser increase in CO during 0 G + CI was entirely caused by a lower heart rate (HR). Thus blood from vascular beds above the legs in seated subjects can alone account for some 50% of the increase in CO during acute 0 G. The remaining increase in CO is caused by a higher HR, of which the origin of blood is unresolved. In supine subjects, CO increased from 7.1 ± 0.7 to 7.9 ± 0.8 l/min (P = 0.037) when entering 0 G, which was solely caused by an increase in HR, because stroke volume was unaffected. In conclusion, blood originating from vascular beds above the legs can alone account for one-half of the increase in CO during acute 0 G in seated humans. A Bainbridge-like reflex could be the mechanism for the HR-induced increase in CO during 0 G in particular in supine subjects.