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The mode of uptake of L-[¹²⁵I]thyroxine by freshly isolated rat liver parenchymal cells was studied by a rapid centrifugation technique. Using conditions for measuring initial rates of uptake, uptake by liver cells was not saturable when exposed to hormone concentrations in the incubation medium ranging from 2 pmol/l to 10 µmol/l. The Arrhenius plot was linear from 2 to 37°C; the temperature coefficient was 1·4. The uptake of L-[¹²⁵I]thyroxine by liver cells was 35% when compared with that of L-[¹²⁵I]tri-iodothyronine. In the presence of 2·8% bovine serum albumin the rate of uptake of L-[¹²⁵I]thyroxine by liver cells was reduced by 90%. These results suggest that L-[¹²⁵I]thyroxine enters the rat liver parenchymal cell by simple diffusion and only the free hormone crosses the plasma membrane.