Abstract Objective: To determine whether major differences in vascular endothelial growth factor secretion exist between adenocarcinomas of the uterine cervix compared with squamous cell carcinomas. Methods: The secretion of vascular endothelial growth factor by eight fresh cervical cancer cell preparations (four adenocarcinomas and four squamous cell carcinomas) and four established squamous cell lines was evaluated using a sensitive enzyme-linked immunosorbent assay in vitro. Results: All cervical tumors secreted significant amounts of vascular endothelial growth factor, and no significant differences between fresh and established squamous cell lines were detectable. In contrast, a highly significant difference in vascular endothelial growth factor secretion was noted between fresh adenocarcinomas (mean = 2712, range between 1700 to 3500 pg/mL/10 5 cells/48 hours) when compared with fresh squamous (mean = 575, range between 200 to 950 pg/mL/10 5 cells/48 hours) or established squamous cervical carcinoma cell lines (mean = 712, range between 400 to 1000 pg/mL/10 5 cells/48 hours) (F-test, P ≤ .001). Conclusion: These data strongly suggest that major differences in the secretion of vascular endothelial growth factor exist between squamous cell carcinoma and adenocarcinomas of the uterine cervix. Therefore, at least some of the differences in the natural biologic behavior of these two histologic types of cervical cancer, including the propensity for earlier lymphatic and hematogenous metastasis as well as the lower response to radiation treatment, could be related to major differences in the secretion of this powerful angiogenic and immunosuppressive cytokine.