Sleep apnea occurs in up to 50% of patients with end-stage renal disease and is improved by nocturnal hemodialysis. We hypothesized that its pathogenesis is related to changes in chemoreflex responsiveness.Twenty-four patients receiving conventional hemodialysis (4h/day, 3 times/week) had overnight polysomnography and measurement of the ventilatory response to carbon dioxide during isoxic hypoxia and hyperoxia using a modified rebreathing technique. Measurements were repeated following conversion from conventional to nocturnal hemodialysis (8h/night, 3–6 nights/week). Patients were divided into apneic and non-apneic groups based on apnea–hypopnea index ⩾15/h at baseline (17 apneics and 7 non-apneics), and the apneic group was further divided into “responders” and “non-responders” based on a significant reduction in AHI at follow-up.Conversion from conventional to nocturnal hemodialysis was associated with a decrease in the ventilatory sensitivity to hypercapnia during hyperoxia in responders (3.2±1.0 vs. 2.3±1.3L/min/mmHg) but not in non-responders (2.8±1.3 vs. 2.9±1.6L/min/mmHg). The change in ventilatory sensitivity was correlated with the change in apnea–hypopnea index in all apneic patients (r=.528, p=0.029).Improvement of sleep apnea following conversion from conventional to nocturnal hemodialysis is associated with a decrease in chemoreflex responsiveness. This finding suggests that increased chemoreflex responsiveness contributes to the pathogenesis of sleep apnea in some patients with end-stage renal disease.