Metabolism of galactose is a specialized liver function. The purpose of this PET study was to use the galactose analog 2-[(18)F]fluoro-2-deoxygalactose (FDGal) to investigate hepatic uptake and metabolism of galactose in vivo. FDGal kinetics was studied in 10 anesthetized pigs at blood concentrations of nonradioactive galactose yielding approximately first-order kinetics (tracer only; n = 4), intermediate kinetics (0.5-0.6 mmol galactose/l blood; n = 2), and near-saturation kinetics (>3 mmol galactose/l blood; n = 4). All animals underwent liver C15O PET (blood volume) and FDGal PET (galactose kinetics) with arterial and portal venous blood sampling. Flow rates in the hepatic artery and the portal vein were measured by ultrasound transit-time flowmeters. The hepatic uptake and net metabolic clearance of FDGal were quantified by nonlinear and linear regression analyses. The initial extraction fraction of FDGal from blood-to-hepatocyte was unity in all pigs. Hepatic net metabolic clearance of FDGal, K(FDGal), was 332-481 ml blood.min(-1).l(-1) tissue in experiments with approximately first-order kinetics and 15.2-21.8 ml blood.min(-1).l(-1) tissue in experiments with near-saturation kinetics. Maximal hepatic removal rates of galactose were on average 600 micromol.min(-1).l(-1) tissue (range 412-702), which was in agreement with other studies. There was no significant difference between K(FDGal) calculated with use of the dual tracer input (Kdual(FDGal)) or the single arterial input (Karterial(FDGal)). In conclusion, hepatic galactose kinetics can be quantified with the galactose analog FDGal. At near-saturated kinetics, the maximal hepatic removal rate of galactose can be calculated from the net metabolic clearance of FDGal and the blood concentration of galactose.