The ability to reversibly decrease probability in response to high-frequency activation, short- term synaptic depression, is a fundamental property of many synapses thought to depend mainly on mechanisms inherent to the presynaptic terminal. We show here that hippocampal glutamate synapses, in the CA1 area of the rat, exhibit a large depression of release probability within seconds following a brief high-frequency burst. This form of short-term synaptic depression affects both recently active synapses (post-burst depression) as well as neighbouring inactive synapses (transient heterosynaptic depression). It is not inherent to the presynaptic terminal, but mediated by astrocytes since it is completely abolished by inhibiting astrocyte metabolism and astrocyte calcium signalling. Our results suggest that the astrocyte part of the tripartite synapse is actively involved in short-term synaptic depression.