In his Discorsi of 1638, Galileo argued that large terrestrial vertebrates would have to grow very thick legs in order to avoid the decreasing cross-sectional area/weight ratios of large objects geometrically similar to small prototypes. Since then, scaling theory (especially the principle of decreasing relative surface area in large forms) has been one of the most widely appreciated and, paradoxically, least studied areas of biology. The two major themes of scaling theory have been: (1) That small and large animals live in different adaptive "worlds" regulated by forces dominant at their size (surface forces for insects, gravity for large organisms). These forces place limits on the size of organic designs (breathing through external tracheae and presence of exoskeleton constrain insects to be small; buckling strength limits the height of trees; scaling of kinetic energy at something close to l(5) sets maximum height of terrestrial bipeds). (2) That small and large animals have characteristic differences in form and function conditioned by the scaling of surfaces and volumes (large animals have relatively smaller brains, thicker legs, lower metabolism, longer life, more convoluted internal surfaces for gas exchange, digestion and circulation). We know that organic form is adapted to body size, but a major issue for space research involves the degree of purely genetic determination for such adaptation. If, as D'Arcy Thompson argued for the trabeculae of the human femur, adaptations to large size require the immediate action of gravitational forces, then prolonged weightless flight will provoke reversion by removal of the necessary stimulus. In any case, we must know what scaling theory predicts (and what animals actually display) in order to predict the potential problems of prolonged weightlessness.