Absolute iron deficiency is treated by correcting the causative lesion and then, traditionally, administering sufficient amounts of ferrous salt to return the haemoglobin level to normal and replenish body stores. The bioavailability of ferric compounds has been questioned and accordingly their therapeutic role remains controversial. A special problem is posed by regular blood donation, where the frequency of phlebotomy is limited by the haemoglobin level, which, in turn, requires maintenance of an adequate supply of iron from dietary sources. Since this latter situation may not always occur, it would be of practical benefit to have a form of supplementation that is effective and can be taken without side effects. These issues were prospectively examined in a consecutive series of otherwise healthy blood donors who developed absolute iron deficiency anaemia and were then randomly allocated to receive 60 mg of this metal as ferrous sulphate twice a day (Group 1: n = 51), 100 mg as chewable ferric polymaltose daily (Group 2: n = 53), or the latter product twice a day (Group 3: n = 55). Serial studies showed that 80% of patients in Groups 1 and 3 had reached normal haemoglobin levels by 12 weeks, but this figure was only 50% in Group 2. Similarly, the proportion of patients improving their percentage saturation of transferrin to within the normal range was significantly better in Groups 1 and 3 than in Group 2 (P < .01). However, body iron stores, reflected in serum ferritin level, was significantly better in Group 1 (P < .01); there was no difference in this respect between Groups 2 and 3. Toxicity was more severe in those receiving ferrous sulphate, with 20% having to discontinue participation owing to nausea and vomiting, whereas this was mild in those receiving ferric polymaltose and none withdrew from the trial for this reason. It can be concluded that the two forms of iron are equally bioavailable for hemoglobin regeneration, but at 12 weeks of study ferrous sulphate was superior in reconstituting stores, as reflected in the serum ferritin level. Since the ferric iron complex is associated with only minimal side effects, it may be useful in selected populations and, in the context of blood donors, valuable as a means of maintaining positive balance, thereby diminishing the number of donors rejected because of their having developed phlebotomy-iron deficiency anaemia. © 1993 Wiley-Liss, Inc.