Regenerative Ca(2+) release from inositol 1,4,5-trisphosphate (IP(3))-sensitive intracellular stores in the form of Ca(2+) waves leads to large-amplitude [Ca(2+)](i) increases in the apical dendrites of hippocampal CA1 pyramidal neurons. Release is generated following synaptic activation of group I metabotropic glutamate (mGlu) receptors. We systematically examined the conditions for evoking these waves in transverse slices from 2- to 3-wk-old rats. Using a sharpened asymmetrical bipolar tungsten stimulating electrode placed in the stratum radiatum, we varied the lateral position of the electrode, the number of stimulating pulses, the train frequency, and stimulus current. Several trends were clear. Increasing the frequency of stimulation from 20 to 100 Hz, keeping the total number of pulses constant, lowered the required stimulus current. Stimulation at frequencies below 20 Hz made it difficult to evoke release. Increasing the number of stimulation pulses, keeping the frequency constant, lowered the threshold current. A minimum of five pulses at 100 Hz was required to evoke release reliably, but several examples of success with three pulses were recorded. Theta-burst stimulation was as effective as tetanic stimulation. Placing the point of the stimulation electrode closer to the pyramidal neuron made it easier to evoke release, although stimulation at a lateral distance of 500 microm with unsharpened electrodes was sometimes successful. The simplest explanation for these results is that a bolus of IP(3) must be produced quickly in a restricted region of the dendrites to generate Ca(2+) waves. The conditions necessary for evoking regenerative Ca(2+) release have many parallels (and some differences) with the conditions required to evoke long-term potentiation in these cells following tetanic stimulation.