During mammalian fertilization, the contact between sperm and egg triggers increases in intracellular Ca2+ concentration ([Ca2+](i)) in sperm. Voltage-gated Ca2+ channels (Ca(V)s) are believed to mediate the initial phase of [Ca2+](i) increases in sperm induced by egg coat (zona pellucida [ZP]) glycoproteins, while store depletion-activated Ca2+ entry is thought to mediate the sustained phase. Using patch-clamp recording and Ca2+ imaging, we show herein that Ca-V channel currents, while found in spermatogenic cells, are not detectable in epididymal sperm and are not essential for the ZP-induced [Ca2+](i) changes. Instead, CATSPER channels localized in the distal portion of sperm (the principal piece) are required for the ZP-induced [Ca2+](i) increases. Furthermore, the ZP-induced [Ca2+](i) increase starts from the sperm tail and propagates toward the head.