Repetitive synaptic stimulation evokes large amplitude Ca(2+) release waves from internal stores in many kinds of pyramidal neurons. The waves result from mGluR mobilization of IP(3) leading to Ca(2+)-induced Ca(2+) release. In most experiments in slices, regenerative Ca(2+) release can be evoked for only a few trials. We examined the conditions required for consistent release from the internal stores in hippocampal CA1 pyramidal neurons. We found that priming with action potentials evoked at 0.5-1 Hz for intervals as short as 15 s were sufficient to fill the stores, while sustained subthreshold depolarization or subthreshold synaptic stimulation lasting from 15 s to 2 min was less effective. A single episode of priming was effective for about 2-3 min. Ca(2+) waves could also be evoked by uncaging IP(3) with a UV flash in the dendrites. Priming was necessary to evoke these waves repetitively; 7-10 spikes in 15 s were again effective for this protocol, indicating that priming acts to refill the stores and not at a site upstream to the production of IP(3). These results suggest that normal spiking activity of pyramidal neurons in vivo should be sufficient to maintain their internal stores in a primed state ready to release Ca(2+) in response to an appropriate physiological stimulus. This may be a novel form of synaptic plasticity where a cell's capacity to release Ca(2+) is modulated by its average firing frequency.