Study objectives: Effects of chronic metabolic alkalosis and acidosis and their relation to central chemoregulation may differ between normocapnic and chronic hypercapnic patients with COPD. The relationship between responses of inspired ventilation (VI), mouth occlusion pressure (P0.1), and cerebral blood volume (CBV), to short-term changes in arterial Pco2 was measured. Patients and methods: Seventeen patients with chronic hypercapnia and COPD(Paco2 > 6.0 kPa) and 16 normocapnic patients with COPD (Paco2 ≤ 6.0 kPa) [FEV1 27% predicted] were studied under baseline metabolic conditions and after 1 week of treatment with oral furosemide, 40 mg/d, or acetazolamide, 500 mg/d. Hypercapnia (change in end-tidal carbon dioxide > 1 kPa) was induced by administering adequate amounts of carbon dioxide in the inspired air. CBV was measured using near-infrared spectroscopy. Results: Compared with baseline metabolic condition, chronic metabolic acidosis and alkalosis did not change ventilatory ($Δ$VI/$Δ$Paco2) and cerebrovascular ($Δ$CBV/$Δ$Paco2) reactivity. Base excess (BE) decreased by 6.8 ± 1.1 mEq/L and 6.9 ± 1.6 mEq/L, respectively, in the normocapnic and chronic hypercapnic COPD groupsduring metabolic acidosis, resulting in a not-quite-significant leftward shift of both the ventilatory and cerebrovascular carbon dioxide response curve. BE increased by 2.3 ± 1.2 mEq/L and 1.2 ± 1.3 mEq/L, respectively, during chronic metabolic alkalosis in both COPD groups, without concomitant shift. Poor correlations between ventilatory and cerebrovascular carbon dioxide responsiveness ($Δ$CBV/$Δ$Paco2 and $Δ$VI/$Δ$Paco2, $Δ$CBV/$Δ$Paco2 and $Δ$P0.1/$Δ$Paco2, respectively) were found irrespective of baseline, respiratory condition, and induced metabolic state. Conclusions: Normocapnic and chronic hypercapnic COPD patients have the same ventilatory and cerebrovascular carbon dioxide responsiveness irrespective of induced metabolic state. © 2002 Elsevier Science Ltd. All rights reserved.