['The effect of simulated spaceflight conditions using the hindlimb unloading model on mucosal immune responses has not been examined. Therefore, we determined whether clearance, protection, and the antibody responses to an enteric pathogen, rotavirus, were altered under simulated spaceflight conditions.', 'Groups of mice were either restrained and hindlimb unloaded, restrained without hindlimb unloading, or housed under standard conditions for either 4 or 14 d prior to and an additional 10 d following inoculation with ECwt murine rotavirus. An additional group of mice previously infected with rotavirus was housed under the three conditions for either 4 or 14 d prior to a rotavirus challenge.', 'Hindlimb unloading of mice did not alter clearance of a primary rotavirus infection compared with controls nor were there differences in protection from rotavirus challenge 42 d later between the three groups, all housed under standard conditions. There were no differences in protection from rotavirus challenge in mice that were hindlimb unloaded during the challenge infection compared with controls. The generation of rotavirus-specific fecal antibodies, as measured by enzyme-linked immunosorbent assay (ELISA), was not significantly different between any of the groups following either primary or challenge rotavirus infection. However, serum rotavirus-specific IgG1 antibody was not induced in mice housed under normal conditions and challenged under hindlimb unloading conditions compared with controls.'] Are kinetics of rotavirus infection in mice altered in a ground-based model of spaceflight?