Extracellular matrix proteins regulate the survival and proliferation of smooth muscle cells. Their effect on airway smooth muscle cell migration is not known. Their role in leukotriene-primed (0.1 microM leukotriene E4) chemotaxis of cultured human airway smooth muscle cells towards platelet-derived growth factor BB (1 ng.mL(-1)) was investigated. Migration of cells was greater on membranes coated with collagens III and V and fibronectin compared to collagen I, elastin and laminin (all 10 microg.mL(-1)). Concentration-dependent promotion of migration was observed on collagen I (1,000>10 microg.mL(-1)), which was associated with increased phosphorylation of Src kinase. This was not observed on laminin or elastin. The role of Src kinase was further confirmed by demonstrating that its inhibitor, PP1 analogue (1 microM), inhibited chemotaxis. Collagen I itself was not a chemoattractant; however, haptokinesis was observed when cells were primed with leukotriene E4, and haptotaxis when cells were primed with platelet-derived growth factor. The priming effect of leukotrienes on chemotaxis was not elicited by promoting adhesion, increasing surface expression of beta1, alphav and alpha5 integrin, or Src kinase phosphorylation. These experiments demonstrate that the extracellular matrix, along with growth factors and cysteinyl leukotrienes, can regulate human airway smooth muscle cell migration. This may be relevant in the remodelling process in chronic airway diseases, such as asthma.