Little is known about the effect of hemodialysis (HD) on gas exchange in subjects with chronic obstructive pulmonary disease (COPD). The purpose of this study was to examine blood gases and pH in COPD patients undergoing HD with bicarbonate dialysate. We studied thirteen subjects with COPD and thirteen controls (CON). All were dialyzed for 4 hrs against a bicarbonate HD solution. Blood gases, pH and HCO(3) (-) were initially analyzed (t(0)) and, during HD, at 30 min (t(0.5)), 1 hr (t(1)) and 4 hrs (t(4)). At t(0), a statistically significant difference was observed for PO(2) (CON: 84.7±3.60, COPD: 72.19±4.92; p<0.001). For the first hr, PO(2) decreased, and at t(1), oxygen was required for 6 COPD subjects. By t(4), there was no significant difference in PO(2) between groups. The alveolar-arterial gradient (ΔA-a) remained different between groups (P<0.001, all times), with increasing ΔA-a for both groups up to t(1) and decreasing over the remaining 3 hr. For both groups, at t(4), ΔA-a was higher than at t(0) (p<0.001). For PCO(2), both groups demonstrated increases from t(0) to t(1) (p=0.0004), with COPD having PCO(2) higher than CON at t(0.5) and t(1) (p<0.05 for both); by t(4), PCO(2) levels decreased to nearly the same as at t(0). Over the 4 hr treatment, HCO(3) (-) and pH increased significantly for both groups; however no significant difference was observed between COPD and CON. Markedly increased ΔA-a is observed during HD in some COPD patients. COPD patients retain more CO(2). However, the effect of HCO(3) (-) leads to mild metabolic alkalosis at t(4).