Much of the difficulty in obtaining precise information of anticipated problems arises from a lack of knowledge of normal mammalian physiology. Many of these deficiencies can be remedied in the laboratory. In space-flight development, however, two distinct investigational approaches can be adopted. The first of these may be characterized as empirical and incremental; that is, the capabilities of the astronaut are explored in successive flights involving relatively modest increases in difficulty or severity of the environmental conditions. In this way it is hoped to ascertain the human limitations without running too great a risk. The second approach can be described as fundamental: determining by a series of controlled experiments the effects of exposure to space-flight conditions upon comparative mammalian physiology, with emphasis on man. A fundamental understanding of the observed effects would be sought so that predictions for new situations and possible ways to control them could be made with confidence. It is not possible now to predict for flights of 30 days or more— (1) The effects of sudden reimposition of reentry accelerations and terrestrial gravity (2) Changes in body fluid distribution and composition (3) The effects of violent physical effort on respiratory and cardiovascular systems in prolonged weightlessness (4) Central nervous system functions, especially coordination, skilled motor performance, judgment, and sleep-wakefulness cycles NASA has emphasized that planning for manned space programs involves a systematic extension from physiological observations in animals to man, and finally the establishment of man as part of the man-vehicle system design. Moreover, these studies require the evaluation of central nervous, cardiovascular, respiratory, gastrointestinal, and other systems as a matrix in mutual interdependence. There is particular interest in the effects of weightlessness on flights exceeding 30 days. Mammalian flights of about 30 days also merit attention, including the development of the life-support systems which must precede such a program. Development of facilities for biological experiments may well be an important requirement for studies in anticipation of manned flights of longer duration than Apollo. Unless the biological satellite programs of the type mentioned above are successful in providing the necessary data, a manned orbiting laboratory may also be important in studies of shorter range. General Studies of Biological Rhythmicity