To identify the Ca 2 + influx pathway responsible for maintaining Ca 2 + oscillations in hamster eggs, changes in intracellular Ca 2 + concentration ([Ca 2 + ] i ) were recorded using the Fura-2 fluorescent imaging technique during iontophoretic injection of inositol phosphates under voltage clamp. Both inositol 1,4,5-trisphosphate (InsP 3 ) and 1,3,4,5-tetrakisphosphate (insP 4 ) caused repetitive Ca 2 + transients when injected continuously into eggs, although the latter was much less effective. These Ca 2 + transients were inhibited by the monoclonal antibody 18A10 to the InsP 3 receptor/Ca 2 + channel 2 + . In Ca 2 + -free medium, InsP 4 -induced Ca 2 + transients were absent or much less frequent than in normal medium. A small but persistent increase in [Ca 2 + ] i during InsP 4 injection was revealed when Ca 2 + up-take into InsP 3 -sensitive Ca 2 + stores was suppressed by thapsigargin. This Ca 2 + rise is due to Ca 2 + entry, but not Ca 2 + release, because it was: (i) increased by raising the extracellular Ca 2 + concentration and abolished in Ca 2 + -free medium; (ii) larger at more negative membrane potentials which provide greater electrical driving force for Ca 2 + entry; and (iii) not affected by 18A10. A moderate dose of InsP 3 did not cause substantial Ca 2 + entry, as tested in thapsigargin- and 18A10-treated eggs. InsP 4 facilitated the restoration of Ca 2 + stores after Ca 2 + releases induced by pulsatile InsP3 injections.Thus, we obtained evidence for a Ca 2 + influx pathway activated by InsP 4 which provides Ca 2 + to refill InsP 3 -sensitive Ca 2 + stores in intact cells.