We sought to investigate if varying levels of bedding had an effect on intra-cage ammonia levels in individually ventilated mouse cages (Euro Standard Types II and III). Employing a routine 2 week cage-changing interval, our goal is to keep ammonia levels under 50 ppm. In smaller cages used for breeding or for housing more than four mice, we measured problematic levels of intra-cage ammonia, and a considerable proportion of these cages had ammonia levels at more than 50 ppm toward the end of the cage-change cycle. These levels were not reduced significantly when the levels of absorbent wood chip bedding was either increased or decreased by 50%. The mice in both cage types II and III were housed at comparable stocking densities, yet ammonia levels in larger cages remained lower. This finding highlights the role of cage volume, as opposed to simply the floor space, in controlling air quality. With the current introduction of newer cage designs that employ an even smaller headspace, our study urges caution. With individually ventilated cages, problems with intra-cage ammonia may go undetected, and we may opt to utilize insufficient cage-changing intervals. Few modern cages have been designed to account for the amounts and types of enrichment that are used (and, in parts of the world, mandated) today, adding to the problems associated with decreasing cage volumes.