Objective: To determine whether serum levels of vascular permeability factor (VPF) are elevated in patients with ovarian hyperstimulation syndrome (OHSS) and to determine if luteinizing granulosa cells may be a source of VPF. Design: Prospective observational study. Setting: University IVF and GIFT program. Patients: Eight consecutive IVF and GIFT patients at high risk for OHSS. Main Outcome Measures: Vascular permeability factor concentration in serum and follicular fluid. Results: Serum VPF was significantly higher (15.2 +/- 4.0 pM; mean +/- SEM) on day +14 in the group who developed severe OHSS compared with those who did not. Follicular fluid VPF (171.5 +/- 18.5 pM) was approximately 100-fold greater than serum (1.7 +/- 1.3 pM) or peritoneal fluid (2.5 +/- 1.3 pM) 36 hours after hCG administration. Conclusion: Vascular permeability factor is elevated in patients with severe OHSS and the ovary may be a source of VPF secretion.