Intravascular CaCl2 infusion in freshwater rainbow trout (Salmo gairdneri) causes a significant degranulation of the corpuscles of Stannius (CS). Concurrently, there is a specific and acute inhibition of whole body Ca2+ influx; Ca2+ efflux is not effected. The material released from the CS after CaCl2 injection consists primarily of a 28-kDa product which we identified as hypocalcin. Electron microscope observations of the CS reveal that type 1 and type 2 cells are degranulated to a similar extent. We conclude that hypocalcin is directly involved in hypocalcemic control in freshwater fish via inhibition of branchial Ca2+ influx, thereby promoting a net loss of Ca2+ across the gill.