The uptake of radioactively labelled hexoses into the cellular space of isolated liver cells has been studied using silicone layer filtering centrifugation. From the hexoses tested, D-glucose is transported most rapidly followed by D-galactose and D-fructose. The rate of L-glucose transport is only 5% of that of D-glucose. This transport enables the concentration of free aldohexoses in the cellular space to reach the external concentration. For D-glucose the rate of transport into the cell largely exceeds the rate of metabolic conversion. This is different with D-fructose where the rate of transport is considerably lower but the rate of metabolism higher. Here the transport may even be a limiting step. The transport of D-glucose and D-galactose shows a saturation characteristic, whereas D-fructose appears not to be saturatable. The Km for D-glucose is found to be 30 mM. All these hexoses compete with each other for transportation. The temperature dependency of D-glucose reveals an activation energy of 22 kcal (92 kJ)/mol (4-18 degrees C) and 7 kcal (29 kJ)/mol (18-37 degrees C). The transport of D-glucose, D-galactose and D-fructose in inhibited by cytochalasin B, phloretin and phlorizin. It is not dependent on Na+ ions. Preliminary results showed no stimulation of the transport by insulin. It is concluded that D-glucose and other hexoses are transported by carrier-mediated diffusion across the plasma membrane of liver cells. This transport shows a large resemblance to the transport of D-glucose into human erythrocytes.