Plasma CO₂ reactions in Pacific spiny dogfish (Squalus acanthias) have access to plasma and gill membrane-associated carbonic anhydrase (CA). Acute severe experimental anaemia and selective CA inhibitors were used to investigate the role of extracellular CA in CO₂ excretion. Anaemia was induced by blood withdrawal coupled to volume replacement with saline. Lowering haematocrit from 14.2 ± 0.4 % (mean ± SEM; N = 31) to 5.2 ± 0.1 % (31) had no significant impact on arterial or venous CO₂ tensions (PaCO₂ and PvCO₂, respectively) over the subsequent 2 h. PCO₂ was maintained despite the reduction in red cell number and a significant 32% increase in cardiac output (V_b), both of which have been found to cause PaCO₂ increases in teleost fish. By contrast, treatment of anaemic dogfish with the CA inhibitors, benzolamide (1.3 mg kg^-1) or F3500 (50 mg kg^-1), to selectively inhibit extracellular CA, elicited rapid and significant increases in PaCO₂, of 0.68 ± 0.17 Torr (6) and 0.53 ± 0.11 Torr (7), respectively, by 30 min after treatment. These findings provide a functional context in which extracellular CA in dogfish contributes substantially to CO₂ excretion. Additionally, the apparent lack of effect of V_b changes on PCO₂ suggests that, in contrast to teleost fish, CO₂ excretion in dogfish does not behave as a diffusion-limited system.