The major problems requiring solution before full-scale evaluation of stroma-free hemoglobin solution (SFHS) in a clinical environment are its high oxygen affinity and relatively short intravascular retention time. Through postmanufacture chemical modification of SFHS we have been able to improve both properties as determined in in vitro and in vivo studies. Permatization of SFHS with pyridoxal 5'-phosphate (PLP) does not affect oxygen-carrying capacity and improves the P50and intravascular retention. This chemically modified hemoglobin is worthy of further evaluation.