Cultures of human lymphocytes were exposed to the mitogen concanavalin A in a low-G environment generated by a fast rotating clinostat. DNA-synthesis was determined by incorporation of 3H-thymidine as the parameter for activation, cell ultrastructure was analyzed by electron microscopy, and cell movements were recorded by a cinecamera. The results were compared with 1-G controls. The cells cultured at low G show: (i) depression of activation by 50%, (ii) appearance of "mitochondria-rich" cells, and (iii) enhanced formation of pseudovilli and uropods. Our investigations in vitro at low and high G and reports on the effect of spaceflights on lymphocytes from cosmonauts and astronauts suggest that hypogravity depresses, whereas hypergravity enhances, lymphocyte activation by mitogens. This study is complementary to an experiment which will study the in vitro activation of lymphocytes in weightlessness during the first Spacelab mission.