Survanta, a natural surfactant, induces an antifibrogenic phenotype and apoptosis in normal human lung fibroblasts (NHLF). As intracellular Ca2+ signalling has been related to programmed cell death, we aimed to assess the effect of Survanta on the intracellular Ca2+ levels in NHLF in vitro. Cultured NHLF were loaded with 5 mM Fura-2 and Ca2+ signals were studied by microfluorimetric techniques. The application of 500mg/ml of Survanta, a concentration which has been shown to exert an apoptotic effect in human fibroblasts, elicited different patterns of Ca2+ signals in NHLF: a) a rapid Ca2+ spike which could be followed by Ca2+ oscillations, and b) a Ca2+ peak followed by a sustained plateau which could be overlapped by Ca2+ oscillations. The initial Ca2+ increase evoked by Survanta was abolished by store depletion by 10mM CPA, blockage of phospholipase C activity with U73122, but not by genisteine, a tyrosine kinase inhibitor. In cells showing a plateau, removal of extracellular Ca2+ caused an immediate decrease of Ca2+ levels to the baseline, confirming that Ca2+ influx took place during the plateau. The plateau was unaffected by La3+, Ni2+, Gd3+, nifedipine and by the selective blockers of store-operated channels BTP2 and 2APB. However, La3+, Ni2+, Gd3+ and BTP2 impaired ATP-induced Ca2+ plateau. These results indicate that Survanta activates a Ca2+ signal through Ca2+ release from intracellular stores mediated by PLC and Ca2+ influx via a yet to unravel pathway.