A number of recent studies have described the presence of significant gastroesophageal reflux (GER) in patients with obstructive sleep apnea (OSA). The aims of our studies were to determine the prevalence of this in a controlled population and to investigate the potential for a causal relationship between the two entities by determining whether therapy of OSA altered GER parameters, and vice versa. All patients presenting to our sleep laboratory for screening polysomnography underwent distal esophageal pH monitoring simultaneously with polysomnography. Control subjects were selected if the apnea-hypopnea index (AHI) was <5.0, and patients were selected if AHI was >15.0. Fourteen subjects with OSA undertook a second polysomnographic study including distal esophageal pH monitoring, with nasal continuous positive airway pressure (nCPAP) intervention. Twelve subjects with proven OSA took part in a randomized, placebo-controlled, double-blinded, parallel group study of the effect of antireflux therapy (nizatidine) on OSA parameters. In 63 patients and 41 controls, we found that patients with OSA had significantly more GER events than controls as measured by number of reflux events over 8 hours (115 vs 23; P <0.001), and percent of time spent at pH <4.0 (21.4% vs 3.7%; P <0.001). In patients with proven OSA, 53.4% of GER episodes were temporally related to apneas or hypopneas. Less than half (46.8%) of all apneas were temporally related to acid reflux, and only 43.8% of arousals were related to reflux events. In the therapeutic trials, nCPAP reduced GER parameters in both patients with OSA and without OSA, suggesting a nonspecific effect. Antireflux therapy (nizatidine) reduced arousals but not apnea-hypopnea index in patients with OSA. Patients with OSA have a higher prevalence of GER than matched control subjects. Nasal CPAP reduces GER parameters nonspecifically, and thus the role of OSA in the pathogenesis of GER remains unclear. GER, however is likely to be important in the pathogenesis of arousals, but there is no evidence that it is involved in the pathogenesis of apneas.