Stimulation of B‐cell antigen receptor (BCR) induces a rapid increase in cytoplasmic free calcium due to its release from intracellular stores and influx from the extracellular environment. Inositol 1, 4, 5‐trisphosphate receptors (IP 3 Rs) are ligand‐gated channels that release intracellular calcium stores in response to the second messenger, inositol 1, 4, 5‐trisphosphate. Most hematopoietic cells, including B cells, express at least two of the three different types of IP 3 R. We demonstrate here that B cells in which a single type of IP 3 R has been deleted still mobilize calcium in response to BCR stimulation, whereas this calcium mobilization is abrogated in B cells lacking all three types of IP 3 R. Calcium mobilization by a transfected G protein‐coupled receptor (muscarinic M1 receptor) was also abolished in only triple‐deficient cells. Capacitative Ca 2+ entry, stimulated by thapsigargin, remains unaffected by loss of all three types of IP 3 R. These data establish that IP 3 Rs are essential and functionally redundant mediators for both BCR‐and muscarinic receptor‐induced calcium mobilization, but not for thapsigargin‐induced Ca 2+ influx. We further show that the BCR‐induced apoptosis is significantly inhibited by loss of all three types of IP 3 R, suggesting an important role for Ca 2+ in the process of apoptosis.