Free iron in the circulation in contrast to iron complexed with protein or carbohyrdate, is intensely toxic. The annual morbidity and mortality from accidental overdose with iron salts is significant and has directed attention to the evaluation of safer forms of therapy. Comparative studies between oral ferrous sulphate and iron polymaltose in rats established an LD100 of 350 mg/kg for the salt, whereas neither morbidity nor mortality could be produced in doses exceeding 1 000 mg/kg for the complex. Bio-availability of iron from salt and complex for haemoglobin synthesis was then compared both in rats and in man with a twin-isotope technique. In experimental animals and in the human studies, venesected individuals were used to reproduce the iron deficiency state where treatment would be indicated. It was concluded that bioavailability is comparable for therapeutic doses of ferrous sulphate and iron polymaltose in iron-deficient subjects. The marginally lower absorption of complex was offset by a greater degree of gastrointestinal tract tolerance; the wide margin of safety may be of importance in reducing the danger of accidental iron overdose.