Many hormones are capable of increasing [Ca2+]i in many different tissues by mobilizing Ca2+ from internal stores, primarily the endoplasmic reticulum, and by promoting Ca2+ influx across the plasma membrane. Recent studies suggest that both processes involve G-proteins. In one case, a G-protein activates a PI 4,5-P2 specific phospholipase C, resulting in the formation of Ins 1,4,5-P3, which then releases Ca2+ from the endoplasmic reticulum. Ca2+ influx can be stimulated by low concentrations of agonist, which do not promote internal Ca2+ mobilization. This process appears to be stimulated directly by a G-protein.