Summary Appropriate control of the affinity of haemoglobin for oxygen is fundamental to the efficient oxygenation of our tissues. Important modifiers of this relationship are pH, CO2 concentration and the intraerythrocytic level of 2, 3-diphosphoglycerate (2,3-DPG). We have studied the influence of haemoglobin affinity on the radiosensitivity of the RIF-1 sarcoma in the mouse. Changes in haemoglobin affinity were induced by exposing donor mice to either 10% oxygen, normal air, or 100% oxygen for 48 h. Blood was drawn from these animals and exchanged transfused into tumour-bearing mice immediately before irradiation. Transfusion of blood from mice breathing 10% oxygen carried a lowered haemoglobin affinity and produced marked radiosensitization of the tumours in the recipients; transfusion with normal blood had no significant effect and transfusions from mice breathing 100% oxygen caused a small increase in radioresistance. Measurements of the level of 2,3-DPG in the blood of these groups showed higher concentrations in the oxygen-deprived animals than in controls but no significant change in animals exposed to 100% oxygen. These results demonstrate that alterations in haemoglobin affinity, probably resulting from changes in 2,3-DPG levels, can have a powerful influence on tumour radiosensitivity. We feel that this mechanism could have considerable clinical importance.The control of oxygen transport by haemoglobin is mediated through allosteric modification of its molecular structure. The best known process involves CO2 which, in binding to haemoglobin to form carbaminohaemoglobin, reduces haemoglobin affinity for oxygen. In addition, CO2 in solution forms bicarbonate which lowers pH and also reduces affinity. These processes are commonly known as the Bohr effect (Bohr et al., 1904) and lead to the advantageous situation in which with every pass through the tissues 02 can be released preferentially whenever the red blood cell encounters regions where CO2 has accumulated and metabolism is rapid. Conversely in the lungs, where CO2 is washed out, haemoglobin affinity is increased facilitating oxygen uptake.More recently the existence of other control systems has been demonstrated (Benesch & Benesch, 1967;Chanutin & Curnish, 1967). The most important of these allosteric modifiers is 2,3-diphosphoglycerate (2,3-DPG) which binds to haemoglobin in a manner which reduces its oxygen affinity. Changes in erythrocyte 2,3-DPG concentration are of fundamental importance in the physiological adaptation to conditions of reduced oxygen availability, such as are encountered at high altitudes or in anaemia (see Thomas et al., 1974, for review (Honig, 1981).The potential importance of this system for the delivery of oxygen to tumours was first recognized by Siemann et al. (1979). In their experiments tumour-bearing mice were exposed to a reduced oxygen atmosphere (12%) for up to 48h before irradiation of the tumours at normal or higher than normal oxygen tensions; this procedure gave tumour sensitization consistent with an approx...