Sex differences have been described in the hepatic transport of many organic anions. Proposed mechanisms include differences in the rate of metabolism, in the degree of binding to cytoplasmic proteins, and in the rate of membrane transport. To better define these factors, we used the perfused rat liver to study the hepatic transport of the glutathione conjugate of sulfobromophthalein (BSP-GSP), a model compound that does not require metabolism for excretion. Hepatic transport of BSP-GSH was saturable for both sexes. Clearance of BSP-GSH from 1% albumin solutions at steady-state was 35-52% greater in female livers than in male livers, and reflected a 47% larger apparent Vmax with no change in the apparent Km. Analysis of the rate of disappearance of BSP-GSH from recirculating perfusate and its appearance in bile using a simple two-compartment model indicated that the ratio of influx to efflux was greater in female livers. These findings are compatible with sex-related differences in the electrochemical driving forces for BSP-GSH uptake.