Pyrodoxylated Polyhemoglobin (PolyHb-PPa) with physiological oxygen affinity (P50 27 mm Hg) was used in vitro and in vivo. The oxygen binding coefficient was 1.1 ml O2/dl/g Hb, the oxygen capacity of 8.5% PolyHb-PPa solution 9.3 ml O2/dl, Hill coefficient 1.7, Met-Hb content below 2%. Exchange transfusion of whole blood with PolyHb-PPa results in a significant, linear increase in total oxygen capacity, in contrast to exchange transfusion with asanguineous solutions. In vitro analysis of oxygen equilibrium curves of mixtures of whole blood with PolyHb-PPa, however, shows a nonlinear release of the additional blood oxygen capacity. Significant amounts of PolyHb-PPa-bound oxygen are made available only when hemodilution exceeds 25%; only at 75% hemodilution does oxygen delivery by PolyHb-PPa account for 50% of the unloaded oxygen. In vivo results after therapy for hemorrhagic shock in minipigs clearly shows the efficacy of oxygen transport by PolyHb-PPa. At 70% hemodilution, PolyHb-PPa bound oxygen was twice that of erythrocytic oxygen. Availability of this additional oxygen capacity was demonstrated by an oxygen extraction ratio of 0.40%. The utility of PolyHb-PPa solution with "normal" P50 in the therapy of moderate anemia, however, remains to be proved.