In the oviduct, cumulus cells that surround the oocyte release progesterone. In human sperm, progesterone stimulates a Ca²⁺ increase by a non-genomic mechanism^,,. The Ca²⁺ signal has been proposed to control chemotaxis, hyperactivation and acrosomal exocytosis of sperm^,,,,. However, the underlying signalling mechanism has remained mysterious. Here we show that progesterone activates the sperm-specific, pH-sensitive CatSper Ca²⁺ channel^,,. We found that both progesterone and alkaline pH stimulate a rapid Ca²⁺ influx with almost no latency, incompatible with a signalling pathway involving metabotropic receptors and second messengers. The Ca²⁺ signals evoked by alkaline pH and progesterone are inhibited by the Ca_v channel blockers NNC 55-0396 and mibefradil. Patch-clamp recordings from sperm reveal an alkaline-activated current carried by mono- and divalent ions that exhibits all the hallmarks of sperm-specific CatSper Ca²⁺ channels^,. Progesterone substantially enhances the CatSper current. The alkaline- and progesterone-activated CatSper current is inhibited by both drugs. Our results resolve a long-standing controversy over the non-genomic progesterone signalling. In human sperm, either the CatSper channel itself or an associated protein serves as the non-genomic progesterone receptor. The identification of CatSper channel blockers will greatly facilitate the study of Ca²⁺ signalling in sperm and help to define further the physiological role of progesterone and CatSper.