The functional effects of the intranasal application of exogenous vasoactive intestinal polypeptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) were evaluated in 12 healthy volunteers before and after neutral endopeptidase (NEP) inhibition with phosphoramidon (PA) and angiotensin-converting enzyme (ACE) inhibition with captopril. The three neuropeptides increased nasal airway resistance (NAR) measured by anterior rhinomanometry and superficial capillary blood flow measured by laser Doppler flowmetry (LDF). After pretreatment of the nasal mucosa with PA, the effects of VIP, SP and CGRP on the LDF signal, NAR and mucus production were potentiated, whereas local pretreatment with captopril did not modify these functional effects. These observations suggest that NEP, but not ACE, may participate in the catabolism of neuropeptides when applied directly to the human nasal mucosa. Furthermore, since these neuropeptides induced nasal obstruction, increased blood flow and rhinorrhea, a decreased activity of the enzymes involved in their degradation could be involved in the physiopathology of rhinitis symptoms.