Cervical intraepithelial neoplasia (CIN) lesions elicit a neovascularization response at the stromal-epithelial junction. In this study, the angiogenic properties of histologically benign cervical epithelium adjacent to CIN were compared to samples of normal cervix from patients with no evidence of CIN. Vessels were detected by immunohistochemical staining for von Willebrand factor (vWf). Expression of a potent angiogenic factor, vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), was measured by in situ hybridization. Statistical comparisons were made using the Student t-test. In histologically benign cervix adjacent to CIN, the microvessel count was significantly increased (164.5 versus 47.3 vessels/cm; p<0.004) and vessels were more closely apposed to the epithelium (15.3 versus 22.4 microm to the basal cell nuclei; p<0.0001) than in normal cervix. Expression of VEGF/VPF was rare in normal cervix but was detectable in more than 90% of sample s of benign epithelium adjacent to CIN. Therefore, vWf staining and VEGF/VPF expression are more sensitive at identifying nearby CIN than conventional histology.