In this in vivo prospective, controlled study, we have examined the capsaicin-induced levels and secretion patterns of the colocalized neuropeptides substance P, calcitonin gene-related peptide (CGRP), and neurokinin A in nasal secretions of subjects with nasal polyps, and we compared these with secretion patterns from healthy subjects and from subjects with allergic rhinitis. Capsaicin was used to elicit neuropeptide release. The neuropeptide levels were measured by an ELISA technique. For substance P, subjects with nasal polyps responded very poorly to capsaicin stimulation. The atopic group was more reactive to capsaicin stimulation than control subjects. For CGRP the increase was immediate in all groups. Atopic subjects and subjects with polyps had a less pronounced but sustained response to capsaicin stimulation. CGRP levels in atopic subjects and those with polyps were restored rapidly. Atopic subjects had higher neurokinin A levels with an immediate and sustained response to capsaicin. Control subjects had higher levels than those with polyps, but both groups were nonresponsive to capsaicin stimulation.