Inositol phosphates have an important role in Ca2+ mobilization and especially inositol 1, 4, 5-trisphosphate (IP3) is now believed to release Ca2+ from the endoplasmic reticulum (ER). On the other hand, the mechanism of activation of Ca2+ entry is unknown. Non-excitable cells have only receptor-operated Ca2+ channels, lacking voltage-operated Ca2+ channels, and are a useful system for studying signal transduction. In this review, some mechanisms for the regulation of Ca2+ entry in non-excitable cells are discussed and a new hypothesis originally proposed by Putney (1986), the capacitative Ca2+ entry model, is focussed. In this model, Ca2+ influx across the plasma membrane is increased when the IP3-sensitive Ca2+ pools is emptied. Capacitative Ca2+ entry is now confirmed in rat parotid acinar cells by studies on the refilling process for intracellular Ca2+ pools and by using the microsomal Ca(2+)-ATPase inhibitor thapsigargin, which does not increase cellular IP3. Finally, capacitative Ca2+ entry is expected to exist in a variety of cell types including excitable cells.