This study was designed to determine the effects of mainstream cigarette smoke (MCS) on stored intraepithelial mucosubstances (IM) and DNA synthesis within the nasal respiratory epithelium of F344 rats and whether such effects persist after cessation of exposure. Rats were exposed to filtered air or diluted MCS for 9 days over a 2-week period. Two hours prior to termination rats were injected with bromodeoxyuridine (BrdU) to label cells synthesizing DNA 1 or 14 days after the last exposure. Sections of nasal tissue blocks taken from a region immediately posterior to the incisor teeth were processed for light microscopy and histochemically stained to detect acidic and neutral IM and immunochemically stained to detect BrdU-labeled cells. The nasal septum was divided into three measurement zones (dorsal, mid-, and ventral) for morphometric quantitation of the volume density of IM and the unit length labeling index (ULLI). MCS-exposed rats terminated 1 day after the last exposure had 270% more IM in the dorsal septum, 58% less IM in the midseptum (due to regions of squamous metaplasia), and amounts of IM in the ventral septum similar to controls. MCS-exposed rats sacrificed 14 days after exposure still had increased amounts of IM in the dorsal septal region, but no regions of squamous metaplasia or amounts of IM in the mid- and ventral septal regions that were different from air-exposed controls. MCS exposure resulted in a significant increase in the ULLI 1 day but not 14 days after exposure in the ventral and midseptal regions only. The results of this study indicate that MCS exposure induces transient alterations in the mucous-producing apparatus in the rat anterior nasal cavity that are resolved following 2 weeks of recovery. However, the type and magnitude of the initial epithelial responses are dependent on the intranasal location of the airway epithelium examined.