Abstract In several types of cells whose cytoplasmic Ca 2+ is regulated by inositol phosphate derivatives, low concentrations of InsP 3 added to permeabilized cell suspensions induce the rapid discharge or part of the InsP 3-sensitive Ca 2+ pool instead of slow monophasic release of Ca 2+ from the entire pool. As a tentative explanation for this puzzling observation, sometimes called ‘quantal release’, it was suggested that the reduced intraluminal Ca 2+ concentration remaining in the Ca 2+ pool after a certain amount of Ca 2+ had been released might allosterically reduce the channels' affinity for InsP 3 and the corresponding InsP 3-dependent Ca 2+ efflux, and thus result in partial pool discharge (Irvine, R.F. (1990) FEBS Lett. 263, 5–9). We have tested this hypothesis by manipulating the Ca 2+ pool contents with ionophore, and found that the rate of InsP 3-dependent Ca 2+ efflux after ionophore-induced partial discharge of the Ca 2+ pools was much faster than what was predicted on the basis of this hypothesis. Heterogeneity of the Ca 2+ pools appears to be a more likely reason for the ‘quantal release’ behavior.