The activation of T lymphocytes, like many cells, requires a rapid rise in intracellular Ca2+ secondary to both an influx and a release from intracellular stores. The latter is activated by inositol-1,4,5-trisphosphate [Ins(1,4,5)P3]. It is controversial if inositol phosphates can also stimulate a plasma membrane Ca2+ channel in T cells. We have studied the human T cell line HPB-ALL which, upon stimulation of its antigen receptor, does not generate detectable levels of Ins(1,4,5)P3 or internal Ca2+ release, but does have a Ca2+ influx. We have reconstituted a receptor-activated Ca2+ transporter from plasma membranes from these cells which has properties similar to the transporter observed in vivo and does not require inositol phosphates for activation. These data show that mitogens may activate more than one type of ligand-gated Ca2+ transport mechanism in T lymphocytes.