Environmental monitoring of microbial contaminants is important for crew health and assessing functionality of engineering systems. Routine monitoring of air and surfaces on the International Space Station found Staphylococcus spp. to be the most common bacterial species whereas Aspergillus spp. were the most common fungi. The levels of microbial contaminants in the air and surfaces were typically low and within the acceptability limits. Bacterial levels in the potable water from the hot water port were uniformly low. Levels in water from the warm port and the SVO-ZV water distribution system exceeded acceptability limits on occasion. Methylobacterium spp. And Ralstonia spp. were the bacteria most commonly isolated from the potable water systems. The space environment, stress, and other factors may also diminish the host immune system. The status of antimicrobial functions of neutrophils and monocytes was determined by flow cytometry. Shuttle astronauts had decreased functionality of NK cells, neutrophils, monocytes, and changes in other elements of immunity. Latent virus reactivation is an important new approach to assessing immunity and can be monitored in body fluids collected during space flight. Reactivation of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella-zoster virus (VZV) was determined by a polymerase chain reaction assay to detect viral DNA. Space flight resulted in increased incidence of EBV and CMV shedding and an increased number of copies of EBV DNA, and the incidence of VZV reactivation increased in astronauts during and after flight. Increased plasma levels of virus-specific antibodies substantiated reactivation of EBV, CMV, and VZV. Increases in cortisol and catecholamines were consistent with elevated stress levels. Cytokines indicative of viral reactivation were elevated. These data indicate that space flight is a unique stress environment that may produce stress-induced changes in immunity that jeopardize the host-microbe relationship.