Signaling through [Ca(2+)](i) is central to regulation of sperm activity and is likely to be the mechanism that transduces signals from the female reproductive tract to regulate sperm motility. In a recent paper1 we showed that exposure of sperm to nitric oxide mobilizes stored Ca(2+) in human sperm, an effect that occurs through nitrosylation of protein thiols. Not only did we find that NO• production by cells of the human female tract would be sufficient to elicit this effect, but progesterone, which is also present in the female tract and is synthesized by the oocyte vestments, acted synergistically with NO• to mobilize Ca(2+) and enhance flagellar beating. Here we argue that a Ca(2+) store at the junction of the sperm head and flagellum is subject to regulation by both progesterone and NO• and that ryanodine receptors at the store may be the point at which coincidence detection and synergistic interaction occurs
