The nasal passages are anatomically complex, and while there have been a number of descriptions of nasal structure in many species, there is very little information available on the distribution of enzymes in the nasal mucosa. In rodents, this delicate mucosa is the first site within the respiratory tract to be exposed during inhalation toxicology studies designed to assess human risks from such exposures. However, the nasal mucosa presents problems for histologic preparation because it is encased in brittle bones. Because of recent interest in the nose as a target site, and findings from biochemical studies which indicate that the nose is very active metabolically, studies were carried out to determine the value of cold glycol methacrylate (GMA) processing for localization of nasal enzymes. For these studies, liver and kidney were used as positive controls. Published histochemical procedures for acid and alkaline phosphatase, adenosine triphosphatase, glucose-6-phosphatase, gamma-glutamyl transpeptidase, and naphthyl butyrate esterase were applied, with modifications, to undecalcified nasal passages of Fisher-344 rats. Frozen sections exhibited excellent enzyme preservation but very poor morphology, while GMA gave good enzyme preservation and excellent morphology. For GMA, acetone fixation generally resulted in the best preservation of enzyme activity. It was concluded that cold GMA processing provides a useful approach to studies of nasal enzyme distribution and that this technique of value for inhalation toxicology studies. Details of enzyme distribution in the squamous, respiratory, and olfactory epithelia, associated glands, and other structures of the nose of the rat are described and discussed.