Striped catfish (Pangasianodon hypophthalmus) are farmed intensively at high stocking densities in Viet-nam where they are likely to encounter environmental hypercapnia as well as occasional high levels ofaquatic nitrite. Nitrite competes with Cl−for uptake at the branchial HCO3−/Cl−exchanger, causing adrastic reduction in the blood oxygen carrying capacity through the formation of methaemoglobin andnitrosylhaemoglobin. Environmental hypercapnia induces a respiratory acidosis where the branchialHCO3−/Cl−exchange activity is reduced in order to retain HCO3−for pH recovery, which should lead to areduced nitrite uptake. To assess the effect of hypercapnia on nitrite uptake, fish were cannulated in thedorsal aorta, allowing repeated blood sampling for measurements of haemoglobin derivatives, plasmaions and acid-base status during exposure to 0.9 mM nitrite alone and in combination with acute and 48 hacclimated hypercapnia over a period of 72 h. Nitrite uptake was initially reduced during the hypercapnia-induced acidosis, but after pH recovery the situation was reversed, resulting in higher plasma nitriteconcentrations and lower functional haemoglobin levels that eventually caused mortality. This suggeststhat branchial HCO3−/Cl−exchange activity is reduced only during the initial acid-base compensation,but subsequently increases with the greater availability of internal HCO3−counter-ions as pH is compen-sated. The data further suggest that branchial Na+/H+exchange plays a significant role in the initial phaseof acid-base compensation. Overall, longer term environmental hypercapnia does not protect againstnitrite uptake in P. hypophthalmus, but instead enhances it. In addition, we observed a significant sizeeffect in nitrite accumulation, where large fish attained plasma [nitrite] above the ambient concentration,while small fish did not. Small P. hypophthalmus instead had significantly higher plasma [nitrate], andhaemoglobin concentrations, revealing greater capacity for detoxifying nitrite by oxidising it to nitrate.