As it has been reported that the depolarization-induced norepinephrine (NE) release is modulated by activation of presynaptic A1-adenosine heteroreceptor and various lines of evidence indicate that A2-adenosine receptor also presents in hippocampus, and that the adenosine effect is magnesium dependent, the present study was undertaken to delineate the role of adenosine receptors in the modulation of hippocampal NE release. Slices from the rat hippocampus were equilibrated with [3H]-NE and the release of the labelled product, [3H]-NE, was evoked by electrical stimulation (3 Hz, 5 V cm-1, 2 ms, rectangular pulses), and the influence of various agents on the evoked tritium outflow was investigated. N6-cyclopentyladenosine (CPA), in concentrations ranging from 0.1 to 10 ㄍM, decreased the [3H]-NE release in a dose-dependent manner without changing the basal rate of release, and these effects were significantly inhibited by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 2 ㄍM) treatment. When the magnesium concentration was reduced to 0.4 mM or completely removed, the evoked NE release increased along with decreased basal rate of release. In contrast, increasing the magnesium concentrations to 2.4 and 4 mM, decreased the evoked NE release. The CPA effects on evoked NE release were reduced by magnesium removal, but potentiated by 2.4 mM magnesium in the medium. 5-(N-cyclopropyl)-carboxamodiadenosine (CPCA, 1 & 10 ㄍM), an A2-agonist, decreased the evoked tritium outflow, and this effect was also abolished by DPCPX pretreatment. CGS, a powerful A2-agonist, did not affect the evoked NE release. However, the effects of CPCA and CGS on evoked NE release were significantly increased by pretreatment of DPCPX in the magnesium-free medium. These results indicate that inhibitory effect of A1-adenosine receptor on NE release is magnesium-dependent, and A2-receptor may be present in the rat hippocampus.