The bioavailability or iron from iron(III)hydroxide polymaltose complex (ferric polymaltose, Fe-PM) was studied in human volunteers with normal or depleted iron stores as well as in patients with iron deficiency anemia. From an oral iron dose of 100 mg neutron activated Fe-PM, starved subjects with depleted iron stores absorbed significantly less (p < 0.003) 59Fe (3.91 +/- 2.24%, mean +/- SD) as compared to the reference, aqueous 59Fe(II) ascorbate solution (13.8 +/- 6.19%). Using non-radiolabeled, commercial Fe-PM no postabsorptive serum iron increase was found after oral Fe-PM (100 mg Fe dosage) in a group of 7 patients with haemorrhagic or posthaemorrhagic iron deficiency anemia. In addition, almost no haemoglobin increase was observed in 9 patients during a 4-weeks treatment period when given Fe-PM (100-300 mg Fe/d) on empty stomach, whereas subsequent treatment with ferrous sulfate (100-200 mg Fe/d) was therapeutically effective (0.15-0.23 g/dl Hb-increase/d). When given 100 or 300 mg Fe/d Fe-PM together with meal, 3 out of 6 patients showed a higher iron utilization rate (3.4-11.9%/d) than given without meal (0.5-7.5%/d). In vitro incubation studies demonstrated that Fe-PM is very stable at neutral pH. A small release of iron from the high molecular weight complex was found only at low pH (< 2). However, high amounts of ionic iron were measured in the reaction tubes after incubating solutions of Fe-PM together with ascorbic acid. This finding could explain the somewhat higher bioavailability of Fe-PM when given with vitamin C containing meals.(ABSTRACT TRUNCATED AT 250 WORDS)