The concentration of red cell 2,3-diphosphoglycerate (2,3-DPG), hemoglobin-oxygen affinity and other oxygen transport variables were determined during first, second and third trimester of normal pregnancy as well as 3 months post partum in 18 healthy women. The median concentration of red cell 2,3-DPG increased significantly from the first to the third trimester (16.1 to 17.0 mumol/gHb, p less than 0.01), whereas 2,3-DPG decreased significantly post partum (p less than 0.01). Normal pregnancy was also associated with relative anemia, a significant increase in arterial pH, hypocapnia and hypophosphatemia. The difference in hemoglobin concentration from the first trimester to 3 months post partum was correlated inversely with the difference in red cell 2,3-DPG content (r = -0.52, p less than 0.05). In spite of the variations in red cell 2,3-DPG, hemoglobin-oxygen affinity expressed as P50 at actual pH remained unchanged during pregnancy and post partum. The study suggests that the increased level of 2,3-DPG during pregnancy may in part represent compensation for physiologic anemia and also compensate for a factor leading to increased hemoglobin-oxygen affinity during pregnancy.