In many cells, receptor activation initiates sustained Ca 2+ entry which is critical in signal transduction 1. Mammalian transient receptor potential (Trp) proteins, which are homologous to the Drosophila photoreceptor-cell Trp protein, have emerged as candidate subunits of the ion channels that mediate this influx. As a consequence of overexpression, these proteins produce cation currents that open either after depletion of internal Ca 2+ stores or through receptor activation 2. However, determining the role of endogenous Trp proteins in signal transduction is complicated by the absence of selective antagonists. Here we examine Trp function during sperm–egg interaction. The sperm acrosome reaction is a Ca 2+-dependent secretory event that must be completed before fertilization. In mammals, exocytosis is triggered during gamete contact by ZP3, a glycoprotein constituent of the egg's extracellular matrix, or zona pellucida (ZP). ZP3 activates trimeric G proteins and phospholipase C and causes a transient Ca 2+ influx into sperm through T-type Ca 2+ channels 3. These early responses promote a second Ca 2+-entry pathway, thereby producing sustained increases in intracellular Ca 2+ concentration ([Ca 2+] i) that drive acrosome reactions 4. Our results show that Trp2 is essential for the activation of sustained Ca 2+ influx into sperm by ZP3.