There are two kinds of evidence for the hypodynamic state: measurement of parameters of circulatory function, and measurement of the response of the individuals to a quantitatively imposed mild gravitational load. After 3 weeks in bed, otherwise healthy persons exhibit an increase of more than 20 percent in heart rate; a reduction of 10 to 20 percent in total blood volume, primarily as a result of reduction of plasma volume; and a decrease in heart size of about 8 percent. Coupled with these cardiovascular changes is a reduction of 10 percent in the basal metabolic rate. It appears as though the circulation and metabolism are reset to a lower functional level commensurate with the reduced demands placed on the whole organism. After 3 weeks of bed rest, all of the subjects tested showed pronounced orthostatic hypotension. After tilting, the average heart rate increased by 37 beats per minute, the systolic blood pressure fell some 12-mm Hg, and some of the subjects fainted. The measurements were continued for 16 days after the bed-rest period, and it was round that recovery was not quite complete when the experiment was terminated. There is little question that in prolonged exposures to the weightless state, there is a fair probability of extensive circulatory adjustments, the seriousness of which cannot yet be foretold. While it is likely that the astronauts will adapt successfully to long periods of weightlessness at some new circulatory functional level, the remote possibility exists that the circulatory changes may be progressive to the point of ultimate failure. Metabolic Effects of Weightlessness Without metabolic information, accurate planning of environmental systems for long flights is difficult. Importance is also attached to early evaluation of weightlessness effects on body-fluid equilibria. The results of Earth orbital flights and of terrestrial water-immersion experiments suggest the occurrence of undesirable changes, although no effects leading to operational incapacity have yet arisen. In both recumbency and immersion, a similar redistribution of body fluids occurs. It has been suggested that recumbency may affect an extracellular fluid-volume receptor mechanism which by decreasing aldosterone secretion by the adrenal gland, would decrease sodium reabsorption by the renal tubules. Aldosterone excretion decreases during recumbency and during standing in water, but increases while standing in air. There is also evidence for cardiac atrial volume receptor mechanisms which respond to increased filling of the left atrium with reflex inhibition of release of pituitary antidiuretic hormone (ADH), resulting in diuresis (Henry-Gauer reflex).