Nitric oxide (NO) is a powerful mediator in the central and peripheral nervous system. In the present study the authors have examined the human nasal mucosa innervation for the presence of the neuronal isoform of the NO-generating enzyme, NO-synthase (NOS), and its correlation with other neuronal mediators and markers by means of double-labeling immunohistochemistry. NOS-immunoreactive nerve fibers were observed to be numerously present around glands and venous sinusoids and, less frequently, around small arteries and veins. Few fibers were seen in the lamina propria. NOS appeared to be frequently colocalized in nerve fibers with vasoactive intestinal peptide and, occasionally, with substance P and tyrosine hydroxylase, a marker for catecholamine biosynthesis. These findings suggest that neurally released NO is an important regulatory mediator of glandular secretion and blood flow in the nasal mucosa.