Effects of hypoxic preconditioning on adenosine (ADO) and its A I receptor were studied in Kunming mice. The ADO content and its metabolites in the brain were measured by a specific enzymatic method; a radioligand binding method was used to study the ADO Al receptor. The ADO content of the hippocampus in group C (exposure to 4 runs of hypoxia) was markedly higher than that in group A (control, without exposure to hypoxia and B (exposure to 1 run of hypoxia), showing that the ADO content could be cumulatively increased in the hippocampus, which was more sensitive to ischemia and hypoxia, during acute and repeated exposure to hypoxia. Al receptor density in group C was significantly lower than in group A and no difference was seen between groups B and C; Al receptor affinity in the hippocampus, pens and medula oblongata in group C was significantly higher than in group A, implying that during hypoxic preconditioning there might be some mechanisms preventing Al receptor density from decreasing further and making Al receptor affinity increase in some brain regions. These results indicate that cumulatively increased ADO in the hippocampus via Al receptor may play a neuroprotective role in the CNS as an inhibitory neuromodulator and thus contribute to the formation and development of acute hypoxic adaptation or tolerance.