In current models describing agonist-induced oscillations in [Ca2+]i, Ca2+ entry is generally assumed to have a simple sustaining role, replenishing Ca2+ lost from the cell and recharging intracellular Ca2+ stores. In cells from the avian nasal gland, a model exocrine cell, we show that inhibition of Ca2+ entry by La3+, SK&F 96365, or by membrane depolarization, rapidly blocks [Ca2+]i oscillations but does so without detectable depletion of agonist-sensitive Ca2+ stores. As the rate of Mn2+ quenching during [Ca2+]i oscillations is constant, Ca2+ entry is not directly contributing to the [Ca2+]i changes and, instead, appears to be involved in inducing the repetitive release of Ca2+ from internal stores. Together, these data contradict current models in that (i) at the low agonist concentrations where [Ca2+]i oscillations are seen, generated levels of Ins(1,4,5)P3 are themselves inadequate to result in a regenerative [Ca2+]i signal, and (ii) Ca2+ entry is necessary to actually drive the intrinsic oscillatory mechanism.