The calyx of Held has recently emerged as a convenient model system to study CNS synapses. In order to understand the mechanisms of synaptic transmission and short-term synaptic plasticity, quantal parameters and their changes should be estimated precisely. For this purpose, various methods have been applied to the calyx of Held synapse. The results confirm many aspects of the early findings on transmission at the neuromuscular junction. On the other hand, the simplest quantal hypothesis does not work at the calyx of Held, because of additional factors such as heterogeneous release probability of synaptic vesicles, intra- and intersite quantal variability, an overlap of facilitation and depression of transmitter release, changes in quantal sizes due to desensitization and saturation of postsynaptic receptors, and delayed clearance of transmitter from the synaptic cleft. These factors should always be taken into account for fully understanding the mechanisms of synaptic transmission and plasticity.