Vascular endothelial growth factor (VEGF) is a multifunctional angiogenic cytokine of importance in inflammation and wound healing but its presence in chronic inflammatory periodontal disease has never been reported. The aims of this study were to investigate the presence of VEGF in human periodontal tissue and gingival crevicular fluid (GCF) in periodontal health and disease. VEGF in tissue was localized by immunohistochemistry. GCF and unstimulated saliva were collected from patients and clinically healthy subjects and VEGF was assessed by using an ELISA. VEGF was detected within vascular endothelial cells, neutrophils, plasma cells and junctional, pocket and gingival epithelium. In periodontitis patients, the volume of GCF and total amount of VEGF collected from diseased sites were both greater than from clinically healthy sites (Wilcoxon test p <0.01). However, the concentration of VEGF per unit volume of GCF was higher at healthy sites compared with diseased sites (Wilcoxon test p <0.05). Higher concentrations of VEGF were detected in healthy sites in patients compared with similar sites in clinically healthy subjects (Mann-Whitney U-test p <0.05). A logistic regression approach indicated that there was variation in VEGF between subjects (p <0.01), and that age (p <0.05), plaque (p <0.05) and pocket depth (p <0.07) were explanatory variables. VEGF was also detected in all saliva samples and was significantly higher in patients than in healthy controls (p <0.05). This study suggests that VEGF could be relevant to angiogenic processes in healthy as well as diseased periodontal tissue and that the periodontal status influences the salivary level of VEGF.