The responses of the cardiovascular system to intensive exercise (hiP) and combined stimuli by hiP and breath-hold (hiP-BH) for 20 s were examined during changing gravity (parabolic flight) and constant gravity (1g). The basic response to microgravity (?g) during low-intensity exercise was an increase in cardiac output (CO) and stroke volume (SV) as a result of augmented venous return. When onset of hiP was superimposed, the initial augmentation of CO and SV were increased further. In contrast, when BH was added, the increases of CO and SV were slowed. We propose that this was due to a transient increase of the pulmonary blood volume with the combination of ?g and BH at large lung volume, creating a temporary imbalance between right ventricular input and left ventricular output. In addition, the BH-induced relative bradycardia may have contributed to a prolongation of the right-to- left indirect ventricular interdependence.