The consequences of adventitious infectious agents upon the interpretation of toxicology studies performed in rats and mice are incompletely understood. Several prevalent murine pathogens cause alterations of the respiratory system that can confuse the assessment of chemically induced airway injury. In some instances the pathogenesis of infection with these agents has been relatively well studied in the lower respiratory tract. However, there are few well-controlled studies that have examined the upper respiratory region, which result in interpretive problems for toxicologic pathologists. The conduct and interpretation of both short-term and chronic rodent bioassays can be compromised by both the clinical and subclinical manifestations of infectious diseases. This paper reviews several important infectious diseases of the upper airway of rats and mice and discusses the potential influence of these conditions on the results of toxicology studies.