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Many factors influence ammonia levels in rodent cages, and high intracage ammonia has been associated with specific types of abnormal nasal pathology in mice. The use of autoclaved corncob bedding and the maintenance of low room humidity reduce the accumulation of ammonia in mouse cages. However, there are no engineering standards that define the limits of ammonia exposure for mice housed in static isolation cages. Regulatory guidance indicates that solid bottom cages must be sanitized at least weekly and that cage components in direct contact with animals must be sanitized at least every 2 wk. Common practice is to replace the bottoms and bedding of static isolation cages once weekly. To determine whether changing static isolation cages once weekly is an appropriate performance standard for mice, we prospectively evaluated the relationship between ammonia levels, nasal histopathology, and housing densities in various grouping strategies of mice housed in static isolation cages. Here, we report that the average nasal pathology score per cage and intracage ammonia levels were correlated, but nasal pathology scores did not differ among mice housed in breeding pairs, breeding trios, or female groups. In light of ammonia levels and histopathology scores as performance standards, these results suggest that a weekly cage-change frequency for static isolation cages does not result in adverse effects. Our results provide evidence to support current practices in the use of static isolation cages for housing laboratory mice in modern vivaria.