Certain functions of immune cells in returning astronauts are known to be altered. T-cell activation requires the interaction of different type of immune cells as T-lymphocytes and monocytes. Cell motility based on a continuous rearrangement of the cytoskeletal network within the cell is essential for cell-cell contacts. In this investigation on the International Space Station we studied the influence of low gravity on different cytoskeletal structures in adherent monocytes and their ability to migrate. J-111 monocytes have been cultured on colloid gold substrateand the the leaving traks used to record the cell motility. A severe reduction of the cell motility was found in low gravity compared to 1g in-flight and ground controls. A qualitative and quantitative analysis of the structures of F-actin, beta-tubulin and vinculin revealed that exposure of momocytes to low gravity affected the distribution of the different filaments and significantly reduced the fluorescence intensity of F-actin fibers. Cell motility relies on an intact structure of different cytoskeletal elements. The reduced motility of monocytes in low gravity must be attributed to the observed severe disruption of the cytoskeletal structures and may be one of the reasons for the dramatic depression of the in vitro activation of human lymphocytes.