It is evident that much remains to be learned about the nasal passages and their responses to toxic materials. For the nose of both laboratory animals and humans, information is needed in the areas of anatomy, physiology, biochemistry, neurobiology, physiopathology, and oncology. This article briefly discussed toxic and neoplastic responses of the nasal passages, and identified a number of issues and questions that provide potentially valuable areas for further research. It was stated that: (1) Histopathologic examination of the nose could profit from the development of a good all-purpose fixative. (2) A consistent and appropriate classification of nasal passageways, epithelia, and other structures is needed to avoid further confusion. (3) A workable scheme for lesion mapping is needed for routine description of lesion distribution in the nasal passages in rodent toxicology studies. (4) Quantitative data are needed concerning regional substrate specificities and kinetics of nasal enzymes in animals and humans for a wide range of enzymes responsible for metabolism of xenobiotics. Moreover, the following questions should be addressed in the future: (1) What is the nature of the progenitor cells in the olfactory epithelium, basal cells alone, or basal and ductular cells? (2) What determines the resistance of regenerated rat olfactory epithelium to subsequent methyl bromide exposure? (3) Can this resistance phenomenon be demonstrated with other olfactory toxicants and in other species? (4) What influence do cage contaminant gases have on olfactory research in laboratories using rodents? The authors also believe that, despite the fact that nasal airflow has been a subject of investigation for many years, much remains to be learned about this complex process. It is expected that the application of computer technology to mathematical modeling of nasal airflow and regional gas uptake will yield significant new information for the understanding of mechanisms responsible for the distribution of upper respiratory tract lesions in animals and humans. The combination of models of regional uptake, wall flux rates, critical biochemical events, nasal blood flow, and other features of nasal physiology, and integration of these models with lower respiratory tract models, will provide valuable tools for investigations of nasal pathology and toxicology. It was also stressed that the effects of toxicants on olfactory function in humans deserve more attention since, in some past studies, it was suggested that the protection afforded by current TLVs against olfactory toxicity may be marginal. A simple and sensitive olfactometric test of general application for toxicology testing in animals remains to be validated.(ABSTRACT TRUNCATED AT 400 WORDS)