People are exposed to a combination of environmental pollutants throughout their lives. Repeated exposures of one common pollutant, ozone, have been reported to cause the development of mucous cell metaplasia in the nasal transitional epithelium (NTE) of rats. The present study was designed to test the hypothesis that exposure to bacterial endotoxin, another toxicant ubiquitous to the environment, potentiates this metaplastic response in rat NTE. Rats were exposed to 0 or 0.5 ppm ozone 8 h/day for 3 days. After ozone exposure, rats were intranasally instilled with saline containing 0 or 100 μg/ml endotoxin once daily for 2 days. Rats were killed 6 h or 3 days after the last intranasal instillation. Nasal tissue was processed for light microscopy and image analysis, or for isolation of total RNA. Mucous cell metaplasia was not detected in air/endotoxin-exposed rats, was observed in ozone/saline-exposed rats, and was most severe in ozone/endotoxin-exposed rats. At 6 h after instillation, amounts of intraepithelial mucosubstances (IM) were 4-fold greater in NTE of ozone/endotoxin-exposed rats as compared to controls. These IM levels were similar to those of ozone/saline-exposed rats. Mucin-specific mRNA (rMuc-5AC) levels were elevated in all treatment groups at this timepoint. At 3 days after instillation, amounts of IM in ozone/endotoxin-exposed rats were 10-fold greater than in controls and 5- fold greater than in ozone/saline-exposed rats. rMuc-5AC mRNA levels remained elevated in the ozone/endotoxin-exposed rats. Despite the fact that bacterial endotoxin alone does not cause a phenotypic change in rat NTE, it can augment the mucous cell metaplasia induced by a previous exposure to ozone.