Anion transport in sickle cells (SS RBC) mediated by the band 3 membrane protein was evaluated by three different measures in both oxygenated and deoxygenated conditions and compared to normal red cells. First, Cl-self-exchange measured as36Cl-efflux at 0°C was normal in SS RBC in both Vmaxand dependence on extracellular Cl-concentration. There was no effect of deoxygenation on either parameter. Second, stilbene-sensitive35SO=4:SO=4exchange, measured at 37°C where morphologic sickling occurred, was also unaffected by deoxygenation and was normal compared to normal red cells. Third, conductive Cl-flux was assessed by measuring the rates of Cl-limited K+efflux in valinomycin-treated cells at 37°C. Both the stilbene-sensitive and insensitive components of net Cl-flux were similar in SS RBC and normal red cells, and were unaltered by morphologic sickling. Thus, despite dramatic alterations in cation transport in SS RBC and the demonstration of interaction between band 3 protein and sickle cell, anion transport functions appear to be normal in SS RBC and are unaffected by deoxygenation. These data suggest that the majority of the anion exchangers in SS RBC are functionally normal.