Using a mathematical model, the effects of water and blood flow inequality on gas exchange in the fish gill were investigated. The results show that O2 exchange is more sensitive to flow inequalities than CO2 exchange. Oxygen exchange is most sensitive to blood flow inequality, whereas carbon dioxide exchange is equally sensitive to inequalities in water and blood flow. Furthermore, it is shown that the effects of flow inequalities cannot be abolished by matching the two flows exactly. The results suggest that the greatest potential for regulation of gas exchange lies on the blood side of the exchanger, and that adjustments in flow distributions to maintain homeostasis in oxygen exchange in the face of changing environmental conditions and/or changing organismic demands, most likely will be accompanied by a change in the acid-base status of the animal.