Changes in [Ca2+]0 are known to affect axonal excitability and synaptic transmission. Ca2+ is also a major component of dendritic action potentials, and changes in [Ca2+]0 may therefore influence dendritic function. Use of the Ca2+-specific ion-selective microelectrode has shown that significant decreases in [Ca2+]0 occur in stimulated neuronal ensembles. Such changes are greatly enhanced during spreading depression and anoxia. The changes appear to be the result of Ca2+ entry into cells during activity, since the diffusion characteristics of Ca2+ in the extracellular space are not unusual. Decreases in [Ca2+]0 would lower the threshold for neuronal excitability but reduce synaptic transmission; rough numerical estimates of these effects are compiled. These are sufficiently large under some conditions to suggest, but not prove, possible modulatory effects of changes in [Ca2+]0. Variation in [Ca2+]0, however, is seen to be a valuable indicator of Ca2+-mediated processes in the nervous system.