Calcium accumulation has been studied in isolated presynaptic nerve terminals from rat brain. Calcium influx is increased when external sodium is replaced by lithium or choline, or when the internal sodium concentration is increased by treatment with ouabain. Calcium efflux is reduced when external sodium is replaced by lithium. The lithium-stimulated calcium accumulation appears to be associated with the nerve terminals, and not with mitochondria or membrane fragments. It is dependent upon an osmotically sensitive surface membrane. The results are consistent with the hypothesis that calcium is actively extruded from mammalian central neurons by a mechanism which exchanges calcium for sodium, and which derives its energy from the sodium concentration gradient.