Vascular endothelial growth factor (VEGF) is a cytokine released by fibroblasts, epithelial cells, and leukocytes that potentiates vascular permeability and growth of new capillaries. Because of these multiple effects, VEGF has been postulated to play a role in the pathogenesis of autoimmune disease, as well as in wound healing. We hypothesized that VEGF was potentially important in mediating the vascular permeability and angiogenesis seen in Crohn's disease, and therefore that VEGF would be increased in the serum of children with Crohn's disease. Serum was obtained from 73 children and young adults with Crohn's disease, 47 with ulcerative colitis, and 29 controls. VEGF levels were measured by enzyme-linked immunosorbent assay. Mean VEGF levels were significantly higher in patients with Crohn's disease (436.4 +/- 37.2 pg/ml) than in ulcerative colitis (306 +/- 41.1 pg/ml) or control (167.8 +/- 29.6 pg/ml) patients. Serum VEGF also correlated significantly with disease activity, being elevated in patients with moderate/severe Crohn's disease and ulcerative colitis. We conclude that serum VEGF is released by inflamed tissues in children with Crohn's disease. This multifunctional cytokine could promote inflammation by increasing vascular permeability or promote wound healing by mediating capillary growth.