Carrier-mediated β-D-hydroxybutyrate transport in brush-border membrane (maternal-sided) vesicles prepared from trophoblast rat placenta was studied. The existence of a carrier-mediated transport system for β-D-hydroxybutyrate in brush-border membrane vesicles was substantiated by the strong inhibitory effect of the protein modifier p-chloromercuriphenyl sulfonic acid and by the saturability of β-D-hydroxybutyrate uptake as a function of β-D-hydroxybutyrate concentration. β-D-hydroxybutyrate uptake was stimulated by the presence of an inward-directed proton gradient but not by an inward-directed Na+gradient. The mechanism for transport of β-D-hydroxybutyrate seems to be a β-D-hydroxybutyrate/H+symport and not a β-D-hydroxybutyrate/OH−antiport because β-D-hydroxybutyrate transport was not sensitive to 4,4-diisothiocyano-2,2‘-stilbenedisulfonic acid or furosemide. The Km, Vmax, and kdcalculated by applying the iteration procedure to the data were 16 mM, 58 nmol. mg−1.10 s−1, and 0 nL.mg−1-s−1, respectively. The β-D-hydroxybutyrate transport system might be shared by other monocarboxylic acids, and the carrier shows reversibility and exchange properties. There were no significant changes in the kinetic parameters of the β-D-hydroxybutyrate transport system during the last 3 d of gestation. Nevertheless, there was a significant increase in the capacity of the β-D-hydroxybutyrate transport system in brush-border membrane vesicles prepared from fasted pregnant rats, suggesting that the rise in maternal ketone body levels occurring as a consequence of maternal starvation is concurrent with the stimulation of the activity of the β-D-hydroxybutyrate placental carrier to supply the fetus with ketone bodies. The signal mediating the stimulation of carrier activity due to starvation remains to be elucidated.(Pediatr Res32: 317–323, 1992)