The ouabain bumetanide resistant (OBR) K+ efflux was investigated in deoxygenated sickle cells in comparison to oxygenated ones, by using a specific inhibitor of the [K+, Cl-] co-transport system, [(DihydroIndenyl)Oxy] Alkanoic acid (DIOA). A DIOA sensitive and a DIOA resistant K+ efflux were measured in deoxygenated sickle cells. The DIOA sensitive K+ efflux shared the properties of the [K+, Cl-] co-transport system, being stimulated by decreased pH and hypoosmolarity. This DIOA sensitive K+ efflux represented 70% of the total K+ efflux at pH 7.0 and at low pO2 (10-15 mmHg). Thus, a small reduction in Ph effectively stimulated the [K+, Cl-] co-transport system in deoxygenated condition, and this may contribute significantly to the sickle cell dehydration. We conclude that at pH lower than 7.4, the [K+, Cl-] co-transport system is permanently activated in sickle cells and leads to sickle cell dehydration in both oxygenated and deoxygenated conditions.