The aim of this study was to examine if nasal secretions contained substance P and/or vasoactive intestinal peptide. Serotonin nasal challenge was performed in 14 normal subjects 15 min after intranasal pretreatment (double-blind) with atropine, methysergide, chlorpheniramine or isotonic saline. Serotonin induced a dose dependent increase in secretion (P less than 0.05), and only pretreatment with atropine reduced the secretion (P less than 0.02). Substance P, measured by radioimmunoassay, was found in all of the examined secretions (n = 100) with a median concentration of 13.7 pmol/l (range 1.7-125.0). Serotonin challenge increased the concentration or content of substance P in a dose-related fashion (P less than 0.01). The different pretreatments did not affect the concentration of substance P. Vasoactive intestinal peptide was found in low concentration in 37% of the secretions with a median concentration of 0 pmol/l (range 0-50.0).