In a study of the functional organization of the cholinergic synapse using the electromotor system of the electric ray, Torpedo marmorata, two main pools of transmitter have been identified: The cytoplasmic, comprising about 20% of terminal acetylcholine, and the vesicular. The latter is morphologically and metabolically heterogeneous. In resting tissue, about 15% of the vesicles have a relatively low transmitter content and density; they are immature (V0) vesicles newly arrived from the cell body by axonal transport. Approximately 35% of vesicles belong to the recycling (V2) pool; these are denser than the main population due to osmotic dehydration attendant upon a reduced osmotic load. The majority (50%) are fully charged ‘reserve’ (V1) vesicles. On perfusion, when axonal replenishment and impulse traffic are alike cut off, V0 and V2 vesicles take up more transmitter and join the V1 pool which now comprises over 90% of all vesicles. On stimulation the V2 population is greatly increased at the expense of V1, but in an ensuing period of rest rejoins the V1 population. Work with isotopically labelled transmitter precursors, false transmitters and endocytotic markers shows that the V2 population is the origin of quantized release. The cytoplasmic pool, however, is also functionally important since it the site of transmitter synthesis for vesicular uptake and is subject to ‘futile recycling’ brought about by the continuous molecular leakage of transmitter into the extracellular space, its hydrolysis by acetylcholinesterase, the uptake of choline and acetate and their resynthesis to acetylcholine. This indicates a control or regulatory function. There is little exchange between this pool and fully changed V1 vesicles but it supplies the recycling vesicles of the V2 pool with transmitter. In this way, quantal size is kept constant and largely independent of cytoplasmic transmitter concentration. In recent years considerable progress has been made in understanding the organization of the cholinergic synapse, largely by intensive work on one particular model system: the electromotor synapses of the electric rays Torpedo marmorata and T. californica. Methods have been devised for isolating functional nerve terminals (synaptosomes), presynaptic plasma membranes, synaptic vesicles and vesiculated fragments (microsacs) of the postsynaptic membrane. From the cell bodies of the electromotor neurones, mRNAs have been isolated that code for presynaptic proteins, and from the target cells (the electrocytes), mRNAs coding for polypeptides comprising or accompanying the receptor. From the latter, using the cDNA technique, Numa and colleagues have deduced the structure of the receptor in great detail. The present lecture will concentrate on the functional organization of the presynaptic nerve terminals.