Two automatic apparatuses utilizing a dual wavelength spectrophotometer were used to perform oxygen dissociation curves on microsamples of blood. The method provides a complete print-out of an oxygen dissociation curve in 15--20 min and the P50 vlues obtained in normal individuals agree closely with those obtained by classical methods. These apparatuses were used to measure oxygen affinity, ie P50, in anemic children with malignant disease prior to treatment and in children undergoing therapy. Red cell 2,3-DPG levels were also measured. In patients with anemia at the time of diagnosis and prior to therapy, the P50 values and 2,3-DPG levels were elevated as is usual in other types of anemia. However, when oxygen affinity and 2,3-DPG levels were measured in anemic patients receiving treatment, three types of response to anemia were noted: 1) increased P50 and 2,3-DPG; 2) normal or low P50 and 2,3-DPG, and; 3) normal or low P50 with increased 2,3-DPG. Patients who adapted poorly to anemia during treatment had usually received prior intensive chemotherapy and transfusion therapy, and their pattern of red cell glycolytic intermediates was consistent with a red cell population with an increased cell age. The failure of some patients to respond to anemia with a decrease in oxygen affinity has implications in regards to the hemoglobin level at which they should be transfused.