THE role of intracellular Ca2+stores during depolarization-evoked Ca2+signals in cultured cerebellar granule neurones was assessed by depletion of the stores with a specific inhibitor of the endoplasmic reticulum Ca2+pump: thapsigargin (TG, 0.7 μM). The maximal rate of [Ca2+]iincrease, measured as the first-order differential of the [Ca2+]itrace, increased directly in proportion to the increasing KCl concentration (in the range 20–90 mM) or, for a given KCl concentration (50 mM), to the levels of pre-stimulation [Ca2+i(range 25–100 nM Ca2+). Both these relationships were unaffected by TG. In contrast, the amplitude of the KCl-evoked response for KCl concentrations > 30 mM (inducing an increase in [Ca2+]i> 400 nM) was increased in the presence of TG.