A confluent endothelial monolayer can be induced to form vascular tubes in response to collagen. We investigated possible mechanisms of collagen-induced tube formation by using antibodies to the VLA-2 integrin receptor and protein kinase C inhibitors. Pre-incubation of cells with anti-VLA-2 (which recognises both the alpha(2) and beta(1) chains) and AK7 (which recognises only the alpha(2) chain) showed a dose-dependent inhibition of tube formation. At 50 mu g/ml, anti-VLA-2 completely inhibited collagen-induced tube formation, whereas AK7 caused only partial inhibition. Both chlorpromazine and trifluoperazine, at concentrations of 1O mu M, prevented tube formation (> 40% inhibition). In summary, the VLA-2 integrin receptor plays a role in the induction of tube formation by type I collagen. Protein kinase C may be activated during this process.