The purpose of this study was to determine the posttransfusion survival of low-affinity red cells (RBCs) containing the hemoglobin modifier, inositol hexaphosphate (IHP). An osmotic pulse technique was used to incorporate IHP, a compound that normally does not cross the RBC membrane. Two groups of six volunteers were studied. RBCs were treated under conditions that resulted in a relatively large increase in mean corpuscular volume (delta MCV = 11.8 +/- 4.0, 1 SD) in Group I, but a relatively small increase (delta MCV = 5.5 +/- 1.9) in Group II. The groups had a similar decrease in mean corpuscular hemoglobin (delta MCH = -3.8 +/- 0.9 for Group I and -3.1 +/- 1.1 for Group II). The 24-hour posttransfusion RBC survival, measured with 3 mL of 51Cr-labeled autologous RBCs, correlated with the induced change in oxygen affinity, and larger shifts were associated with poorer survival. An acceptable 75-percent 24-hour posttransfusion survival was achieved for p50 increases up to approximately 15 torr. Cells that survived 24 hours appeared to have a normal lifespan. This study is the first demonstration of adequate survival for human RBCs with a potentially long-lasting decrease in oxygen affinity.