Utilization - economic and regulatory issues: the impact of blood substitutes on blood banking world wide; potential use of red blood cells substitutes within the military; blood substitutes - unique regulatory aspects. Fundamental principles of oxygen transport : oxygen transport, oxygen carriers, and the transfusion trigger; microcirculatory consequences of blood substitutes with haemoglobin solutions; efficacy of perfluorocarbon-based emulsion as a temporary oxygen carrier; pathophysiology of oxygen utilization in haemorrhagic shock - studies with human recombinant haemoglobin. Interactions with organ systems: immunological alterations following haemorrhagic shock - considerations for resuscitation with blood substitutes; the effect of haemoglobin-based substitutes on kidney function; interactions of haemoglobin with the central nervous system. Interactions with molecular species: interactions between haemoglobin and bacterial endotoxin In Vitro and In Vivo. Alternative strategies and indications: encapsulation of haemoglobin in liposomes; the use of blood substitutes in tumour therapy; human haemoglobin derived from transgenic swine - a starting material for `blood substitute` formulations. Clinical development: OptroTM (recombinant human haemoglobin) - a therapeutic for the delivery of oxygen and the restoration of blood volume in the treatment of acute blood loss in trauma and surgery; production, characterization, and clinical evaluation of hemolinkTM on o-raffinose cross-linked haemoglobin-based blood substitute; hemassistTM - development and clinical profile; the clinical development of human polymerized haemoglobin; oxypureTM - development of polymerized bovine haemoglobin; febluobronTM - development of an oxygen carrying perfluobronTM - development of an oxygen carrying perfluorocarbon. Future directions: future perspective of red cells substitutes.