Background: Angiogenesis is a critical factor in the progression of solid tumors, including cervical cancers. The mechanisms reponsible for angiogenesis in cervical neoplasia, however, are not well defined. Purpose: Our goal was to determine the relationship between angiogenesis and the expression of the angiogenic cytokine vascular permeability factor (VPF), also known as vascular endothelial growth factor, and its receptors in cervical neoplasia. Methods: Sixtysix cervical biopsy specimens were evaluated; among these, 16 samples were designated as benign, 17 as low-grade squamous intraepithelial lesions, 18 as high-grade squamous intraepithelial lesions, and 15 as invasive squamous cell carcinomas. Histologic sections immunostained for factor VIIIrelated antigen were evaluated quantitatively for microvessel density and for the presence of epithelial stromal vascular cuffing. Sections were also evaluated for VPF messenger RNA (mRNA) expression by in situ hybridization. Results: VPF mRNA expression, epithelial stromal vascular cuffing, and microvessel density counts were significantly increased in invasive carcinoma and in high-grade intraepithelial lesions as compared with lowgrade intraepithelial lesions and benign squamous epithelium. Vascular cuffing and increased microvessel density counts were also significantly associated with increased VPF mRNA expression. Conclusions: These observations suggest that VPF is an important angiogenic factor in cervical neoplasia. [J Natl Cancer Inst 87:1237-1245,1995]