The initial bronchoconstrictor response of the asthmatic airway depends upon airway smooth muscle(ASM) contraction. Intracellular calcium is a key signalling molecule, mediating a number of responses including proliferation, gene expression and contraction of ASM. Ca²⁺ influx through receptor operated calcium(ROC) or store operated calcium(SOC) channels is thought to mediate longer term signals. The mechanisms of SOC activation in ASM remain to be elucidated. Recent literature has identified the STIM and ORAI proteins as key signalling players in the activation of the SOC subtype; calcium release activated channel current (I_CRAC) in a number of inflammatory cell types. However the role for these proteins in activation of SOC in smooth muscle is unclear. We have previously demonstrated a role for STIM1 in SOC channel activation in human ASM (HASM). The aim of this study was to investigate the expression and define the potential roles of the ORAI proteins in SOC associated Ca²⁺ influx in HASM cells. Here we show that knockdown of ORAI1 by siRNA resulted in reduced thapsigargin (TG) or cyclopiazonic acid (CPA) induced Ca²⁺ influx, without affecting Ca²⁺ release from stores or basal levels. CPA induced inward currents were also reduced in the ORAI1 knockdown cells. We propose that ORAI1, along with STIM1 are important contributors to SOC entry in ASM cells. These data extend the major tissue types in which these proteins appear to be major determinants of SOC influx, and suggest that modulation of these pathways may prove useful in the treatment of bronchoconstriction.