Serum inorganic phosphorous was decreased significantly on the third postoperative day following cardiac surgery in 18 patients initially studied. Reduced plasma inorganic phosphate has been shown to cause a reduced concentration of red cell organic phosphates, an important determinant of hemoglobin-oxygen affinity. Therefore, 10 consecutive patients were studied to determine if reduced 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) concentration and increased hemoglobin-oxygen affinity accompanied the fall in serum inorganic phosphate concentration. A significant fall in 2,3-DPG and an increase in hemoglobin-oxygen affinity was present in red cells of patients studied on the first postoperative day. A reduction in red cell ATP was also present and persisted for 5 days during which time red cell 2,3-DPG returned to levels which were in excess of preoperative values. The reduction in serum inorganic phosphorous followed the reduction in red cell 2,3-DPG and correlated with the reduction in ATP. The latter changes may indicate the diversion of glucose and more specifically 1,3-DPG into the RapoportLeubering pathway away from ATP generation at the phosphoglycerate kinase step and the utilization of plasma inorganic phosphate for 2,3-DPG resynthesis. Neither the transfusion of stored blood nor the effect of cardiopulmonary bypass fully explained the reduction in red cell 2,3-DPG and the inefficiency of hemoglobin function postoperatively. Further studies in postsurgical patients are needed to clarify the cause of the changes observed since they are potentially deleterious, especially in the subject with compromised cardiovascular and pulmonary function.