INOSITOL-1,4,5-trisphosphate (InsP(3))-induced Ca2+ release is a key mechanism for intracellular Ca2+ mobilization(1). The rate of Ca2+ release declines progressively with time until a higher concentration of InsP(3) is added, which is referred to as the incremental detection mechanism(2). Two hypotheses have been postulated to explain these complex kinetics : (1) Ca2+ stores consist of multiple compartments (quanta) with different sensitivities to InsP(3) (refs 3-7), and (2) the rate of Ca2+ release is modulated by the Ca2+ concentration in the lumen of Ca2+ stores(8-12). We studied this phenomenon by real-time measurement of the luminal Ca2+ concentration of Ca2+ stores using a Ca2+-sensitive fluorescent dye, but our results were not explained by either of these hypotheses. Here we report that the complex kinetics of Ca2+ release results from the heterogeneous density of equally InsP(3)-sensitive channels on the Ca2+ stores. This heterogeneity creates Ca2+ stores with apparently different sensitivities to InsP(3), which may have different functions in Ca2+ mobilization.