Abstract The distribution of substance P-immunoreactive and calcitonin gene-related peptide–immunoreactive nerve fibers in the nasal mucosa was compared between normoxic and chronically hypoxic rats (10% O 2 and 3.0–4.0% CO 2 for 3 months). In the normoxic nasal mucosa, substance P- and calcitonin gene-related peptide–immunoreactive nerve fibers were found within and under the epithelium and around the glands and blood vessels in the lamina propria. These immunoreactive fibers have many varicosities. In the chronically hypoxic nasal mucosa, the relative density of intra- and subepithelial substance P-immunoreactive and calcitonin gene-related peptide–immunoreactive fibers and those in the lamina propria was higher than in normoxic mucosa. The length of substance P-positive fibers within the chronically hypoxic olfactory and respiratory epithelium was 1.66 and 2.45 times higher than within the normoxic epithelium, respectively. The length of calcitonin gene-related peptide-immunostained fibers within the chronically hypoxic olfactory and respiratory epithelium was 1.56 and 1.84 times higher, respectively. Because substance P and calcitonin gene-related peptide are the predominant signal peptides of primary sensory neurons, the increased number of these fibers may represent enhanced sensory mechanisms in the hypoxic nasal mucosa. In addition, considered together with the findings in chronically hypoxic tracheal mucosa, the increased density of intraepithelial fibers containing substance P and calcitonin gene-related peptide suggests that this is a predominant feature of hypoxic adaptation throughout the upper and lower respiratory tracts.