Adenosine is a widespread neuromodulator which can be directly released in the extracellular space during sustained network activity or can be generated as the breakdown product of ATP. Whole cell patch clamp recordings were performed from CA3 principal cells and interneurons in hippocampal slices obtained from P2-P7 neonatal rats in order to study the modulatory effects of adenosine on giant depolarizing potentials (GDPs) which constitute the hallmark of developmental networks. We found that GDPs were extremely sensitive to the inhibitory action of adenosine (IC₅₀= 0.52 µM). Adenosine contributed also to the depressant effect of ATP as indicated by DPCPX-sensitive changes of ATP-induced reduction of GDPs frequency. Similarly, adenosine exerted a strong inhibitory action on spontaneous glutamatergic synaptic events recorded from GABAergic interneurons and on interictal bursts which developed in CA3 principal cells after blockade of GABAA receptors with bicuculline. All these effects were prevented by DPCPX indicating the involvement of inhibitory A1 receptors. In contrast, GABAergic synaptic events were not changed by adenosine. Consistent with the endogenous role of adenosine on network activity, DPCPX per se, increased the frequency of GDPs, interictal bursts and spontaneous glutamatergic synaptic events recorded from GABAergic interneurons. Moreover, the adenosine transport inhibitor NBTI and the adenosine deaminase blocker EHNA decreased GDPs frequency thus providing further evidence that endogenous adenosine exerts a powerful control on GDPs generation. We conclude that, in the neonatal rat hippocampus, the inhibitory action of adenosine on GDPs is due to the negative control of glutamatergic, but not GABAergic inputs.