Synaptic transmission in the brain generally depends on action potentials. However, recent studies indicate that subthreshold variation in the presynaptic membrane potential also determines spike-evoked transmission. The informational content of each presynaptic action potential is therefore greater than initially expected. The contribution of this synaptic property, which is a fast (from 0.01 to 10 s) and state-dependent modulation of functional coupling, has been largely underestimated and could have important consequences for our understanding of information processing in neural networks. We discuss here how the membrane voltage of the presynaptic terminal might modulate neurotransmitter release by mechanisms that do not involve a change in presynaptic Ca(2+) influx.