The mode of operation of synaptic transmission has been primarily worked out at the vertebrate neuromuscular junction, thus providing a framework for the interpretation of studies at central synapses. However, differences have been found between the two systems, and a coherent model is still lacking for central synapses. Research in this area revolves around several questions. (1) Is the variability of quantal amplitudes determined pre- or postsynaptically? (2) What is the occupancy of postsynaptic receptors following the release of a synaptic vesicle? And (3) does multivesicular release occur at single release sites following one presynaptic action potential? To answer these questions, it is essential to investigate synaptic processes at the level of single release sites. This is technically difficult because of the complex morphology and small dimensions of central synapses. Nevertheless significant advances have been made in the past few years.