Pathophysiological differences in neural responses to hypertonic saline were investigated in acute sinusitis (n=25), chronic fatigue syndrome subjects with nonallergic rhinitis (n=14), active allergic rhinitis (n=17) and normal (n=20) subjects. Increasing strengths of hypertonic saline were sprayed into their nostrils at 5 min intervals. Sensations of nasal pain, blockage and drip increased with concentration and were significantly elevated above normal. These parallels suggested activation of similar subsets of afferent neurons. Urea and lysozyme secretion were dose dependent in all groups suggesting that serous cell exocytosis was one source of urea after neural stimulation. Only allergic rhinitis and normal groups had mucin dose responses and correlations between symptoms and lysozyme secretion (R²=0.12-0.23). The lysozyme dose responses may represent axon responses in these groups. The neurogenic stimulus did not alter albumin (vascular) exudation in any group. Albumin and mucin concentrations were correlated in sinusitis suggesting that nonneurogenic factors predominated in sinusitis mucous hypersecretion. Chronic fatigue syndrome had neural hypersensitivity (pain) but reduced serous cell secretion. Hypertonic saline nasal provocations identified significant, unique patterns of neural and mucosal dysregulation in each rhinosinusitis syndrome.