The sex difference in the hepatic uptake of tetrabromosulfonephthalein (TBS) was investigated in male and female rats in two different experimental models. In the intact animal, the initial plasma disappearance constant rate, the initial velocity of uptake, and the plasma clearance of TBS were significantly higher in females than in males. In sinusoidal liver plasma membrane vesicles, kinetic parameters of TBS uptake were investigated in both sexes. The Km was lower in females than in males (5.5 +/- 0.4 vs 17 +/- 4 microM, P < 0.05), whereas Vmax showed comparable values (544 +/- 15 vs 581 +/- 60 nmol TBS/min/mg protein, mean +/- SD, NS, females and males, respectively). Collectively, these data indicate that the sex difference in hepatic uptake of TBS is located at the sinusoidal liver plasma membrane and is due to a greater affinity of the electrogenic transport system(s) in females.