VEGF-induced vascular barrier disruptions, formation of fenestrae and vesiculo-vacuolar organelles (VVOs), are involved in enhancing vascular permeability in metastatic and edematous diseases. Here, we analyzed vascular permeability enhanced by VEGFs with different receptor selectivity using biological and ultrastructural methods. VEGF-A(165), which stimulates both FIt-1 and KDR, induced the formation of both fenestrae and VVOs at a similar rate, while VEGF-F, a KDR-specific VEGF vammin, predominantly induced the formation of fenestrae with an approximately 5-fold more potent vascular permeability response than VEGF-A165. This is the first report showing that VEGFs with different receptor selectivity evoke distinct changes in vascular ultrastructure. (C) 2008 Elsevier Inc. All rights reserved.