Echocardiographic measurements of astronaut cardiac function have documented an initial increase, followed by a progressive reduction in both left ventricular end-diastolic volume index and stroke volume with entry into microgravity (m-G). The investigators hypothesize that the observed reduction in cardiac filling may, in part, be due to the absence of a gravitational acceleration dependent, intraventricular hydrostatic pressure difference in m-G that exists in the ventricle in normal gravity (1-G) due to its size and anatomic orientation. This accelerationdependent pressure difference, DPLV, between the base and the apex of the heart for the upright posture can be estimated to be 6660 dynes/cm2 (" 5 mm Hg) on Earth. DPLV promotes cardiac diastolic filling on Earth, but is absent in m-G. If the proposed hypothesis is correct, cardiac pumping performance would be diminished in m-G. To test this hypothesis, ventricular function experiments were conducted in the 1-G environment using an artificial ventricle pumping on a mock circulation system with the longitudinal axis anatomically oriented for the upright posture at 45 to the horizon. Additional measurements were made with the ventricle horizontally oriented to null DPLV along the apex-base axis of the heart as would be the case for the supine posture, but resulting in a lesser hydrostatic pressure difference along the minor (anterior-posterior) axis. Comparative experiments were also conducted in the m-G environment of orbital space flight on board the Space Shuttle. This paper reviews the use of an automated cardiovascular simulator flown on STS-85 and STS-95 as a Get Away Special payload to test this hypothesis. The simulator consisted of a pneumatically actuated, artificial ventricle connected to a closed-loop, fluid circuit with adjustable compliance and resistance elements to create physiologic pressure and flow conditions. Ventricular instrumentation included pressure transducers in the apex and base as well as immediately upstream of the inflow valve and downstream of the outflow valve, and a flow probe downstream of the outflow valve. By varying the circulating fluid volume, ventricular function could be determined for varying preload pressures at a regulated, mean afterload pressure of 95 mm Hg. This variation in preload condition permitted the construction of a ventricular function curve for the m-G environment for comparison to the same curve for the 1-G environment. Data were collected from both missions at the upper end of the ventricular function curve. Experiment operation in the 1-G, supine orientation or in the m-G environment eliminated the DPLV observed in the 1-G, upright orientation. Consistent with the hypothesis, additional atrial pressure was required in m-G to obtain stroke volumes and flow rates similar to those measured in 1-G for the upright posture. The necessary increase in atrial pressure was approximately 5 mm Hg in these experiments. In the same range of flow rates and stroke volumes, similar flows were observed in the 1-G supine posture for atrial pressures intermediate to the 1-G upright and m-G values, also consistent with the hypothesis. Additional experiments on board the Space Shuttle are in preparation to gather data across the rest of the normal physiologic range of the ventricular function curve.