This paper summarizes the lower body negative pressure experiments performed in space, beginning with the experiments conducted on Skylab, because this program provided the most cardiovascular physiology data for United States space flight. Data obtained during studies of lower body negative pressure for use as a countermeasure after months of Russian space flight are also presented. Lower body negative pressure experiments conducted aboard Space Shuttle flights provide data about the deadaptation response of the cardiovascular system to orthostatic stress occurring during periods of zero gravity, and about protection against postflight orthostatic intolerance. Data obtained using Russian and American lower body negative pressure devices indicate that, when a crew member stands, as opposed to being supported by a seat or saddle as in the American device, there may be a slight detrimental effect in terms of the cardiovascular response to this orthostatic stress. Comparison of heart rate and blood pressure response to entry and landing of the Shuttle indicate that, although lower body negative pressure is a different stress and is applied in a different manner, the maximum heart rates during lower body negative pressure are reached at approximately the same point that the maximum heart rates are reached during entry and landing. Thus, the use of a lower body negative pressure stress in flight is a fairly good predictor of the cardiovascular response to the actual entry and landing of the Shuttle.