Recent advances in metallohistochemistry have substantiated the identification of a distinct class of neurons in the brain, the zinc-containing neurons. These neurons sequester peculiar amounts of zinc in their presynaptic boutons and show both high-affinity uptake and calcium- and impulse-dependent release of the cation. It is thought that the zinc may act to stabilize the storage of certain macromolecules in presynaptic vesicles, but there is also mounting evidence that zinc released from vesicles can produce a broad spectrum of neuromodulatory effects upon target cells. Zinc-containing neurons are found predominantly in limbic and cerebrocortical regions, and a possible role of these neurons in the modification of synaptic strength is considered.