Quantal size can be altered experimentally by numerous treatments that seem to lack any common thread. The observations may seem haphazard and senseless unless clear distinctions are made from the outset. Some treatments shift the size of the entire population of quanta. These quanta are released by nerve stimulation. Other treatments add quanta of abnormal size or shape--monstrosities--to the population (4.0). Usually, perhaps even invariably, the monstrosities are not released by nerve stimulation. 6.1. POPULATION SIZE INCREASES. 6.1.1. Quantal size must be regulated. The size of the entire quantal population can be experimentally shifted to a larger size, with the mean rising two- or even four-fold. Before these observations, it was reasonable to suppose that quantal size was relatively fixed, with little room for maneuver. A logical picture is that synaptic vesicles have a maximum transmitter capacity, and usually they are filled to the brim. This picture is wrong. The quantity of transmitter packaged in the quantum must be regulated by the neuron, so depending on circumstances, quantal size can be increased or decreased. Figure 18 makes the case for regulation more strongly than words. We are beginning to identify some of the signals for up and down regulation, and the first steps have been made in discovering the signal transduction pathways, but we are far from a true understanding. This is hardly surprising, because our information about how transmitter molecules are assembled into quantal packages is still imperfect. Until we understand the engine, it may be difficult to picture the accelerator or the brake. 6.1.2. Signals that up regulate size. Stimulation of the presynaptic neuron increases quantal size at the NMJ, at synapses in autonomic ganglia and in hippocampus. The stimulus parameters necessary to elicit the quantal size increase have not been explored sufficiently in any of these cases, and all deserve further investigation. At both frog and mouse NMJs quantal size is roughly doubled following exposure to hypertonic solutions, which elevate the rate of spontaneous quantal release. This discovery, coupled with the increases caused by tetanic stimulation, suggested that the signal for up regulation is a period of greatly enhanced quantal output. The size increase takes about 15 min in hypertonic solution in mouse and about 60 min in frog. Highly hypertonic solutions do not increase the rate of quantal release in frog; they also do not increase quantal size. This supported the idea that quantal release rate is the signal for up regulation.(ABSTRACT TRUNCATED AT 400 WORDS)