The effects of phloretin, H2DIDS (4,4'-diisothiocyano-1,2-diphenylethane-2,2'-disulfonate) and SO4-2 on anion transport in Ehrlich ascites tumor cells was studied in an effort to determine whether Cl- and SO4-2 share a common transport mechanism. Sulfate, in the presence of constant extracellular Cl- (100 mM), reduces Cl- self-exchange by 43% (40 mM SO4-2) and Cl--SO4-2 exchange by 36% (25 mM Cl-/O SO4-2 compared to 25 mM Cl-/50 mM SO4-2). Phloretin blocks without delay and to the same extent the self-exchange of both Cl- and SO4-2. For example, at 10(-4) M phloretin, anion transport is inhibited 28% which increases to 78% at 5 X 10(-4) M. Reversibly bound H2DIDS also inhibits the self-exchange of both Cl- and SO4-2. However, at all H2DIDS concentrations tested (0.5 - 10 X 10(-5) M) SO4-2 transport was far more susceptible to inhibition than that of Cl-. H2DIDS when irreversibly bound to the cell inhibits SO4-2 but not Cl- transport. The results of these experiments are consistent with the postulation that both Cl- and SO4-2 are transported by a common mechanism possessing two reactive sites.