Adenosine is a CNS depressant with both pre- and postsynaptic actions. Presynaptically, adenosine decreases neurotransmitter release in the hippocampus but only at excitatory terminals. In the thalamus, however, we show that, in addition to its actions at excitatory synapses, adenosine strongly suppresses monosynaptic inhibitory currents both in relay cells of the thalamic ventrobasal complex (VB) and in inhibitory neurons of the nucleus reticularis thalami (nRt). A concomitant increase in transmission failures and results coefficient of variation analysis are both consistent with a presynaptic mechanism. Pharmacological manipulations support an A1 receptor-mediated process. Slow thalamic oscillations induced in vitro by extracellular stimulation and recorded with extracellular multiunit electrodes in VB and nRt are dampened by adenosine without affecting their periodicity. We conclude that adenosine can presynaptically down-regulate inhibitory postsynaptic responses in thalamus and exert robust antioscillatory effects, likely by synergistic depression of both excitatory and inhibitory neurotransmitter release.