The frequency at which mouse cages are changed has important implications for the animals, animal care personnel, and facility managers. The objective of this study was to determine how bedding volume and the interval between changes affect microenvironmental conditions, health, and behavior of mice housed in individually ventilated cages (IVC). A total of 15 cages (n = 5 cages per bedding volume) housing ICR female mice (n = 5 animals per cage) were monitored for 17 d. Parameters monitored included clinical evaluation of each animal, appearance of the cage, fecal corticosterone levels, bedding weight, and mouse mass. Atmospheric analysis was performed daily to determine intracage ammonia cage humidity and temperature on a daily basis. Mice were videotaped for 10 min on days 1, 8, and 15, and videos were analyzed for abnormal behaviors. On day 17, 1 mouse from each cage was euthanized, and bronchoalveolar lavage was performed. Statistical differences in parameters were most often noted between low- and high-volume bedding groups. Correlation between visual appearance and actual intracage environmental conditions and mouse health and behavior at specific time points indicated cages that appear dirty to most observers did not have measurably adverse effects on the animals for any of the many parameters evaluated in this study. This study demonstrated that a 2-wk interval between cage changes for ICR female mice housed in IVC caging (with approximately 90 air changes per hour) and aspen chip bedding did not significantly affect measures of animal well-being in this study. This lack of effect occurred despite the appearance of excessive soiling by the 2-wk time point.