Considerable research over the past three decades has been devoted to characterizing changes in the response of cells of the immune system to stimuli while exposed to altered gravity conditions. A consistent finding shows that mammalian cells subjected to conditions of spaceflight and the microgravity environment of space manifest a number of alterations in structure and function. Changes in cells flown on the space shuttle include reduction in growth activation and decline in growth rate in the total population. Other changes include chromosomal aberration, inhibited locomotion, altered cytokine production, changes in protein kinase C distribution, and increased apoptosis. Human lymphocytes respond poorly to mitogenic stimulation in microgravity and lymphoid cell lines are growth arrested. Recent research into the gene expression of immune cells under altered gravity conditions has provided insight into the possible pathways involved in adapting to gravity changes. Here we synthesize the findings of research related to changes in the immune response as a result of exposure to altered gravity conditions.