We have recently demonstrated that the severity of sleep-disordered breathing in obstructive sleep apnoea hypopnoea syndrome (OSAHS) can be reduced by lowering the surface tension (γ) of the upper airway lining liquid (UAL). Morning xerostomia (related to oral breathing during sleep) is reported by most OSAHS patients. In the present study we examine relationships between breathing route, oral mucosal ‘wetness’ and the γ of UAL. We studied eight healthy subjects (age, 25 ± 5 years [mean ±S.D.]; body-mass index, 23 ± 2 kg m−2) during a 120 min challenge of both nasal-only breathing (mouth taped) and oral-only breathing (nose clip), each on a separate day (randomized). Both oral mucosal ‘wetness’ (5 s contact gravimetric absorbent paper strip method) and the γ (‘pull-off’ force technique) of 0.2 μl samples of UAL obtained from the posterior pharyngeal wall were measured at 15 min intervals (mouth tape removed and replaced as required). Upper airway mucosal ‘wetness’ increased during 120 min of nasal breathing from 4.0 ± 0.4 (mean ±S.E.M.) to 5.3 ± 0.3 μl (5 s)−1 but decreased from 4.5 ± 0.4 to 0.1 ± 0.2 μl (5 s)−1 with oral breathing (both P < 0.001, repeated-measures ANOVA, Tukey's multiple comparison test, post hoc test). Concurrently, the γ of UAL decreased from 59.3 ± 2.2 to 51.8 ± 0.98 mN m−1 with nasal breathing but increased from 64.4 ± 2.7 to 77.4 ± 1.1 mN m−1 with oral breathing (P < 0.001). For the group and all conditions studied, γ of UAL values strongly correlated with upper airway mucosal ‘wetness’ (correlation coefficient, r2=−0.34, P < 0.001; linear regression). We conclude that oral breathing increases and nasal breathing decreases the γ of UAL in healthy subjects during wakefulness. We speculate that nasal breathing in OSAHS patients during sleep may promote a low γ of UAL that may contribute to reducing the severity of sleep-disordered breathing.