OBJECTIVE To assess the potential involvement of vascular endothelial growth factor in the hyperpermeability characterizing the ovarian hyperstimulation syndrome (OHSS). METHODS A controlled clinical study that followed the kinetics of vascular endothelial growth factor in the plasma of patients with severe OHSS from the time of admission to the hospital and until clinical resolution. METHODS Women hospitalized with severe OHSS in a tertiary medical center. METHODS Seven patients with severe OHSS after ovulation induction for IVF and seven controls who had received a similar ovulation induction regimen and did not develop the OHSS. METHODS Three blood samples were obtained from each OHSS patient: upon hospitalization for severe OHSS, when significant clinical improvement was evident, and on the first follow-up visit after the patients' discharge. Ascitic fluid was obtained from all OHSS patients by therapeutic paracentesis during the active phase of the syndrome. Blood samples were drawn from the control patients 4 to 6 days after ET. All samples were assayed for vascular endothelial growth factor levels, hematocrit, E2 levels, and white blood cell count. METHODS Vascular endothelial growth factor levels were assayed by ELISA. Estradiol was determined by RIA. RESULTS Compared with the controls, high levels of vascular endothelial growth factor were detected in the plasma of all patients admitted for severe OHSS. Levels dropped significantly along with clinical improvement, reaching minimum values after complete resolution. A statistically significant correlation was found between plasma vascular endothelial growth factor levels and certain biologic characteristics of OHSS and of capillary leakage such as leukocytosis and increased hematocrit. Ascitic fluid obtained from the study patients also contained high vascular endothelial growth factor levels. CONCLUSIONS These findings suggest the involvement of vascular endothelial growth factor in the pathogenesis of capillary leakage in the OHSS.