From Fisons Pharmaceuticals Limited, Holmes Chapel, Cheshire SYNOPSIS A method is described for measuring the plasma unsaturated iron-binding capacity in the presence of very high concentrations of iron as iron-dextran. The procedure utilizes 59Fe to label the apotransferrin with subsequent separation of ionic iron from transferrin-bound iron on an ion exchange or Sephadex G.25 column.The unsaturated iron-binding capacity has been measured in rabbits and dogs after intravenous injection of iron-dextran and in human subjects after total dose infusion of iron-dextran. No evidence of saturation of the unsaturated iron-binding capacity was found even when the plasma iron values were greater than 40,000 .tg Fe/100 ml.The treatment of iron-deficiency anaemia by a single intravenous infusion or injection of the total iron requirements in the form of iron-dextran is now an established technique. It has been described by several authors (Basu, 1963; Bonnar, 1965;Marchasin and Wallerstein, 1964;Dawson, Goldthorp, and Spencer, 1965) and is generally called 'total dose infusion' (TDI).It is essential that when any iron preparation is introduced into the bloodstream in such quantities (2-3 g as Fe) no large amounts of ionic iron should be precipitated or released. There is no precipitation of iron from iron-dextran (Imferon2) over a wide pH range in plasma and none of the proteins at iron concentrations of up to 5% (Golberg, 1958). The slow clearance over several days of iron-dextran from the bloodstream after TDI gives an indication of its stability in blood (Marchasin and Wallerstein, 1964).It has been shown in studies in vitro (Fielding and Smith, 1963) that at high concentrations of iron-dextran haemolysis of red blood cells can take place. They attributed this to the presence of ionic iron and calculated that around 0-3 % of the total iron was in this uncomplexed state. Using polarographic and electrophoretic techniques it has been demonstrated that atpH 5 *6, 1 to 2 %of the total iron in iron-dextran is present in the ferrous state,