Sleep apnea (SA) occurs in up to 50% of patients with end-stage renal disease (ESRD) and is improved by nocturnal hemodialysis (NHD). This study tested the hypothesis that its pathogenesis is related to altered chemoreflex responsiveness (CRR). Patients receiving conventional hemodialysis (CHD) underwent overnight polysomnography and assessment of CRR using a re-breathing technique. Measurements were repeated 3-6 months following conversion from CHD to NHD. Patients were divided into apneic and non-apneic groups based on an apnea-hypopnea index (AHI) >15/hr on CHD and apneic patients were further divided into "responders" and "non-responders" based on >50% reduction in AHI with NHD. Conversion to NHD was associated with a significant decrease in CRR in apneic responders but not in non-responders and non-apneic patients. In conclusion, improvement of SA by NHD is associated with a decrease in CRR. This suggests that increased CRR contributes to the pathogenesis of SA in patients with ESRD.