The extracellular matrix (ECM) influences a variety of cellular functions, including survival, adhesion molecule expression, differentiation and migration. The ECM composition of the epithelial basement membrane is altered in asthmatics. In this study we elucidate the major survival signals received by bronchial epithelial cells in vitro by studying the effects of a variety of ECM factors and soluble growth factors on bronchial epithelial cell survival. Our findings indicate that the insulin family of soluble growth factors provide important survival signals but also that adhesion to ECM is a crucial determinant of bronchial epithelial cell survival. In the BEAS 2B bronchial epithelial cell line, collagens I and IV, laminin, fibronectin and vitronectin provide significant levels of protection from apoptosis. Tenascin-C has no effect, whereas elastin and collagen V increase apoptosis to above control levels. BEAS 2B cells secrete their own biosynthesized matrix (BSM), which also provides rescue from apoptosis. Protection by collagen I, fibronectin and vitronectin was found to be via an RGD domain. Laminin, collagen IV and BSM mediated survival is not RGD-dependent. Primary bronchial epithelial cells (HBECs) exhibit a similar pattern of apoptosis rescue to the BEAS 2B cell line although we did not observe any vitronectin-mediated protection in the primary cells. These data indicate that bronchial epithelial cell survival is dependent both on soluble growth factors and on a variety of ECM-derived signals.