At fertilization in mammals the sperm activates development of the oocyte by inducing a prolonged series of oscillations in the cytosolic free Ca ²⁺ concentration. One theory of signal transduction at fertilization suggests that the sperm cause the Ca ²⁺ oscillations by introducing a protein factor into the oocyte after gamete membrane fusion. We recently identified this sperm-specific protein as phospholipase Cζ (PLCζ), and we showed that PLCζ triggers Ca ²⁺ oscillations in unfertilized mouse oocytes. Here we report that microinjection of the complementary RNA for human PLCζ causes prolonged Ca ²⁺ oscillations in aged human oocytes that had failed to fertilize during in vitro fertilization or intracytoplasmic sperm injection. The frequency of Ca ²⁺ oscillations was related to the concentration of complementary RNA injected. At low concentrations, PLCζ stimulated parthenogenetic activation of oocytes. These embryos underwent cleavage divisions and some formed blastocysts. These data show that PLCζ is a novel parthenogenetic stimulus for human oocytes and that it is unique in its ability to mimic the repetitive nature of the Ca ²⁺ stimulus provided by the sperm during human fertilization.