Studies are proposed on the regulation of cytoplasmic calcium levels in the nervous system in terms of membrane transport and sequestration within intracellular organelles. The concentraton of calcium ions in the cytoplasm is vitally important to nerve cells, for these ions not only influence axonal conduction but appear to be a crucial factor governing release of neurotransmitters at the synapse. Attention here is focused on calcium disposition at the nerve ending, studied in synaptosomes and in isolated ganglia. Experiments are proposed to characterize the factors regulating both influx and efflux across the plasma membrane in terms of the modes of transport and the sensitivity to various modifiers. Binding to and sequestration within intracellular organelles, in particular the mitochondrial of the nerve ending, will be examined quantitatively for comparison with the processes at the plasma membrane. Emphasis is on the mechanisms involved in transporting and storing the ions, on the regulatory processes governing these mechanisms, and on the modifiers that can and may influence calcium disposition.