Functions of secretoneurin include chemotaxis for monocytes and endothelial cells, and inhibition of endothelial cell proliferation. Inhibition of monocyte chemotaxis by staurosporine indicated involvement of specific signaling mechanisms. We have tested effects of kinase inhibitors on activation of endothelial cells for neutrophil adherence by secretoneurin. Pretreatment of endothelial cells by secretoneurin induced in endothelium increased adhesiveness to neutrophils. Addition of staurosporine, an inhibitor of protein kinase C, completely abolished endothelial cell activation, whereas tyrphostin-23, a tyrosin kinase inhibitor, had no effect. Results on activation of neutrophil-endothelial cell adherence by secretoneurin demonstrate that specific signaling mechanisms are involved in endothelial cell activation.