Experiments during spaceflight and its groundbase analog, bedrest, provide consistent data which demonstrate that numerous changes in cardiovascular function occur as part of the physiological adaptation process to the microgravity environment. These include elevated heart rate and venous compliance, lowered blood volume, central venous pressure and stroke volume, and attenuated autonomic reflex functions. Although most of these adaptations are not functionally apparent during microgravity exposure, they manifest themselves during the return to the gravitational challenge of earth's terrestrial environment as orthostatic hypotension and instability, a condition which could compromise safety, health and productivity. Development and application of effective and efficient countermeasures such as saline "loading," intermittent venous pooling, pharmacological treatments, and exercise have become primary emphases of the space life sciences research effort with only limited success. Successful development of countermeasures will require knowledge of the physiological mechanisms underlying cardiovascular adaptation to microgravity which can be obtained only through controlled, parallel groundbased research to complement carefully designed flight experiments. Continued research will provide benefits for both space and clinical applications as well as enhance the basic understanding of cardiovascular homeostasis in humans.