ATP is known as a potent neuromodulator in the cerebellar cortex. It enhances the frequency of spontaneous postsynaptic currents (sPSC frequency) recorded from Purkinje neurons by 104 ± 13% (n = 61). The ATP-induced increase of the sPSC frequency is mediated mostly by inhibitory interneurons. This effect was blocked by the P2 receptor antagonist PPADS (10 mM), which also uncovers a tonic activation of P2 receptors, because it decreased the frequency to 75 ± 4% (n = 29) by itself. A block of ecto-ATPases with ARL67156 (50 mM) revealed a tonic ATP release in the cerebellar cortex. An effect of adenosine was not observed on the sPSC frequency. On the other hand, ATP and adenosine decreased the amplitude of evoked postsynaptic currents at the parallel fiber -Purkinje neuron synapse. This decrease was abolished in the presence of the A1 receptor antagonist DPCPX (2 mM) and was strongly reduced when the non-hydrolysable ATP-analogon ATPgS was applied, suggesting an adenosine A1 receptor-mediated effect. Our results suggest that ATP and adenosine play important roles in reducing the output of the cerebellar cortex in different ways. ATP strengthens inhibition onto the Purkinje neuron by an increase of the activity of inhibitory interneurons, while adenosine, a degradation product of ATP, reduces excitatory inputs from granule cells. Supported by the DFG (DE19-1) and the B.I.F.