A reduced diffusing capacity for carbon monoxide (DCO) is common among patients with chronic thromboembolic pulmonary hypertension (CTEPH) and often persists for more than a year following successful pulmonary thromboendarterectomy (PTE). To determine the relative contribution the pulmonary membrane diffusing capacity (DM) and pulmonary capillary blood volume (VC) make to the reduction in DCO, we measured both in 29 patients with CTEPH before and approximately 3 weeks after PTE. Mean preoperative DM was reduced in patients with CTEPH (28 mL min-1 mm Hg-1 vs 43 mL min-1 mm Hg-1 in control subjects; p < 0.001) and dropped significantly following PTE (21 mL min-1 mm Hg-1; p < 0.001). Mean preoperative VC was mildly reduced in the CTEPH group compared with healthy control subjects (57 vs 67 mL; p = 0.044) and did not rise following PTE (57 mL pre-PTE vs 54 mL post-PTE; p > 0.05) despite substantial reduction in mean pulmonary artery pressure and increase in cardiac output after surgery. We conclude that the low DCO observed in patients with CTEPH before and after PTE is principally caused by a reduced DM and to a lesser extent by a low VC. The mechanisms responsible remain speculative but may reflect pathophysiologic changes in the pulmonary microcirculation caused by chronic pulmonary hypertension that did not improve in the postoperative period studied.