The present study was initiated to investigate the effects of hypertonic saline (15%) or low pH (1 M lactic acid, pH 2) applied to the human nasal mucosa. Patients suffering from birch-pollen allergy, which had been de-sensitized with capsaicin, were compared to non-treated, healthy controls. Five patients were pre-treated with an intranasal, unilateral application of 30 microM capsaicin for 15 min during three consecutive days. Six weeks later we applied 50 microliters of hypertonic saline (15%) to the inferior turbinate on the capsaicin-pre-treated side of the patients as well as to the controls. Symptom score, using a visual analogue scale (VAS), and the cross-sectional area of the nasal cavity were measured bilaterally using acoustic rhinometry at different intervals. The same procedure was repeated one week later with lactic acid. Provocation with lactic acid and hypertonic saline caused a significantly higher symptom score in controls as compared to capsaicin-pre-treated patients. Furthermore, application of lactic acid caused a significant reduction in cross-sectional area of the nasal cavity suggesting vasodilatation in controls compared to capsaicin-pre-treated patients. The reactions to hypertonic saline were generally lower but the differences in symptom score between capsaicin-pre-treated and non-treated persons remained. The results implies that capsaicin-sensitive afferents are involved in low pH- and hypertonicity-mediated reactions in the human nasal mucosa. Furthermore, local capsaicin de-sensitization causes a very long-lasting loss of sensory reactivity to these agents.