Hyperoxia and alkalemia, as a result of pulmonary hyperventilation and elevation of plasma DNA (pDNA), are seen during the first 24 h after ischemic stroke. In this study we have examined the correlation between pDNA and these blood parameters in health and stroke. Acid-base equilibrium, oxygen status, hemoglobin affinity to oxygen and concentration of pDNA in arterial blood were measured after the intravenous injection of homologous long-chain DNA to healthy rats and rats subjected to common carotid arterial occlusion. In addition the effect of adding homologous DNA to human and rat venous blood samples was studied in vitro. Hyperoxia, alkalemia, and an increase in hemoglobin affinity to oxygen were seen in rats with artificial stroke. A marked decrease in pulmonary hyperventilation and hemoglobin affinity to oxygen was observed after injection of homologous genomic DNA (10(-6) g/mL of blood). After the DNA injection, blood gas measurement and concentration of pDNA were correlated. Addition of DNA at a concentration of 10(-7) g/mL to venous blood samples in vitro increased oxygen saturation that disappeared when the dose of the DNA increased 10-fold. Thus, a change of pDNA concentration or size can alter acid-base equilibrium, oxygen status, and oxygen transport. These results may be important for a better understanding of the mechanisms of stroke and other diseases associated with the elevation of pDNA concentration, and they open the possibility of new therapeutic approaches.