The magnocellular oxytocin and vasopressin neurones of the hypothalamus are now understood in exceptional detail. Extensive quantitative details from many independent sources are available describing the electrical activity of the neurones in diverse circumstances, the subcellular localization of vesicles, and rates of hormone secretion from nerve endings into the blood and from dendrites into the brain. These data enable the relationship of electrical (spike) activity to vesicle exocytosis to be inferred with some precision. Such calculations lead to the conclusion that exocytosis of peptide-containing vesicles is a relatively rare event even in this vesicle-dense system. At any given release site in the neurohypophysis, it seems that several hundred spikes are needed on average to release a single vesicle. Release from compartments within the brain seems also to be very rare, making it implausible that peptides can act in a temporally precise, anatomically specific manner. However, very large amounts of peptide are released by these infrequent events, consistent with their likely role as neurohormonal messengers.