The relationship between alterations in cerebral blood volume (CBV) and central chemosensitivity regulation was studied under neutral metabolic conditions and during metabolic acidosis. Fifteen healthy subjects (56±10 years) were investigated. To induce metabolic acidosis, ammonium chloride (NH4Cl) was given orally. CBV was measured using Near Infrared Spectroscopy during normo- and hypercapnia and related to inspired ventilation (V̇i). A mean acute metabolic acidosis of $Δ$pH -0.04 was realized with a mean decreased arterialized capillary PCO2 (PcCO2) of 0.20 kPa (1.5 mmHg) (both P<0.001). During normocapnia, CBV was 3.51±0.71 and 3.65±0.56 ml 100 g-1 (mean±S.D.), measured under neutral metabolic conditions and during acute metabolic acidosis, respectively (ns). Corresponding values of V̇i were 7.6±1.4 and 10.0±2.4 l min-1 (P<0.01), respectively. The slopes of the CO2-responsiveness ($Δ$CBV/$Δ$PcCO2 and $Δ$V̇i/$Δ$PcCO2), were not significantly different during both metabolic conditions. A significant correlation between $Δ$CBV/$Δ$PcCO2 and $Δ$V̇i/$Δ$PcCO2 was found during metabolic acidosis (P<0.01), but not under neutral metabolic conditions. CBV does not contribute in a predictable way to the regulation of central chemoreceptors. Copyright © 2001 Elsevier Science B.V.