The expression of vascular endothelial growth factor (VEGF), a specific mitogen for endothelial cells, was examined in salivary glands and in normal saliva. In normal salivary glands, VEGF mRNA and protein were strongly present in acinar cells, whereas little or no VEGF was found in ductal cells. In chronically inflamed glands, VEGF protein was in addition present in ductal elements and in infiltrating mononuclear cells. No difference of VEGF expression was observed between benign and malignant salivary gland tumours. By ELISA, whole saliva of 24 healthy individuals contained up to 2.5 ng/ml (mean 1.4 ng/ml; SD 0.77 ng/ml) of VEGF, confirming the constitutive secretion of this cytokine by human salivary glands. Western blot analysis of normal saliva under non-reducing conditions detected anti-VEGF reactive protein moieties of approximately 46 kD, corresponding to VEGF secreted by cells in tissue culture. Additional anti-VEGF reactive proteins of approximately 60 and 90 kD were detected in the saliva of some individuals. The presence of considerable quantities of VEGF in normal human saliva suggests an important role for this cytokine in the maintenance of the homeostasis of mucous membranes, with rapid induction of neoangiogenesis by salivary VEGF helping to accelerate wound healing within the oral cavity. Moreover, salivary VEGF may permeabilize intraglandular capillaries and thus participate in the regulation of saliva production itself.