Upper airway obstruction in patients with sleep apnea may occur in the absence of a negative intraluminal upper airway pressure. We hypothesized that surface tension forces may play a role in the pathogenesis of obstructive sleep apnea (OSA), and that a topical soft tissue lubricant might reduce the severity of OSA. Ten male patients (age 49 +/- 10 yr [mean +/- SD]; body mass index [BMI] 31 +/- 5 kg/m2) with OSA (apnea-hypopnea index [AHI] 17 +/- 9) were studied. The arousal index was lower with the lubricant treatment than with placebo (mean difference 8; 95% CI 4 to 11 arousals/h; p = 0.001). The AHI was lower, in each of the 10 patients, on the lubricant treatment than the placebo (mean change 10, 95% CI 6 to 13; p = 0.0003). The lower AHI with lubricant as compared with placebo was present in both supine (mean difference 13; 95% CI 5 to 20; p = 0.006) and nonsupine (mean difference 6; 95% CI 0 to 12; p = 0.05) positions. There was no significant difference in sleep architecture between the lubricant and placebo treatments. Application of a topical lubricant consistently reduced the severity of OSA. This implies a pathogenetic role for surface tension forces in OSA, and a potential role for surface tension-reducing agents in the treatment of OSA.