Humans, as well as other life forms, have developed on earth under the terrestrial gravitational field. Questions concerning the effect of the gravity vector changes on the animal physiology have begun to emerge only in the last decades. Physiological alterations were observed during space flights, but space-born investigations at cellular levels are still very limited. Earth-bound simulations of low gravity obtained with the 3-dimensional Random Positioning Machine are extensively utilized to explore the effects of microgravity on cell function. After only a few minutes, weightlessness affected the cytoskeleton of lymphocytes, astrocytes, neurons and testicular cells, disorganizing microtubules, intermediate filaments and microfilaments. Cell division was impaired, mitochondria were disrupted and apoptotic phenomena occurred. Expression of proteins involved in transmembrane ion and water transport were also affected. In the Leydig cells the key enzymes (3beta- and 17beta-hydroxysteroid dehydrogenases) leading to testosterone synthesis were depressed. However, after 20 h of clinorotation the cells were able to synthesize heat shock proteins that initiated protection and recovery. The cytoskeleton was again well organized, normal mitosis occurred and the percentage of apoptotic cells returned to the range of 5%, similar to the control cultures. Ion and water transmembrane proteins and steroid dehydrogenases returned to normal levels. Long-term experiments showed that low gravity induced only transient alterations in the cultured cells, which were able to adapt to the gravity vector changes and to regain normal activity. These data may explain the physiological adaptation occurring in astronauts during and after space flights.