Inositol 1,4,5-trisphosphate receptors (IP₃Rs) release calcium ions, Ca²⁺, from intracellular stores, but their roles in mediating Ca²⁺ entry are unclear. IP₃ stimulated opening of very few (1.9 ± 0.2 per cell) Ca²⁺-permeable channels in whole-cell patch-clamp recording of DT40 chicken or mouse B cells. Activation of the B cell receptor (BCR) in perforated-patch recordings evoked the same response. IP₃ failed to stimulate intracellular or plasma membrane (PM) channels in cells lacking IP₃R. Expression of IP₃R restored both responses. Mutations within the pore affected the conductances of IP₃-activated PM and intracellular channels similarly. An impermeant pore mutant abolished BCR-evoked Ca²⁺ signals, and PM IP₃Rs were undetectable. After introduction of an α-bungarotoxin binding site near the pore, PM IP₃Rs were modulated by extracellular α-bungarotoxin. IP₃Rs are unusual among endoplasmic reticulum proteins in being also functionally expressed at the PM, where very few IP₃Rs contribute substantially to the Ca²⁺ entry evoked by the BCR.