To test whether anesthetics alter hemoglobin O2 affinity, venous blood was sampled from 27 healthy subjects before and during general anesthesia for appendectomy with halothane, enflurane, or nitrous oxide anesthesia. 0.110-ml aliquots of blood were equilibrated in microtonometers at 37 degrees C with known PO2 levels in gases containing 0%, 0.5%, 1%, 2%, or 3% halothane, 0%, 1%, 2%, 3%, or 4% enflurane, or 60% N2O. pH was then measured and PO2 corrected to pH = 7.4. Saturation was determined spectrophotometrically (Radiometer OSM-2). P50 computed from this PO2 and measured saturation was increased 5% (P less than 0.01) when blood was tonometered with N2O, but not in blood samples taken during N2O anesthesia and then equilibrated without N2O. Halothane and enflurane had no effect. 2,3 DPG was not affected by any agent. The authors conclude that inhalational agents in use today do not cause the oxygen dissociation curve to change in a way which might jeopardize the patient's oxygenation.