Vascular endothelial growth factor (VEGF), a key regulator of blood vessel function during angiogenesis, has been related to various diseases including atherosclerosis, neurodegenerative disorders and cancers. However, data about genetic determinants of its concentration in blood are scarce. The present study aimed at estimating additive genetic heritability, household component effect and the influence of 3 common VEGF polymorphisms on plasma VEGF concentration. A random sub-sample of 160 nuclear families (647 individuals), aging from 5 to 57, was obtained from the Stanislas Family Study. Plasma VEGF concentration was measured by a multiplexing ELISA and genotyping of the polymorphisms C(-460)T, G(405)C and C(936)T of the VEGF gene was carried out by RFLP. After adjustment for the influence of known environmental covariates, significant familial correlations were observed for plasma VEGF concentration (P< or = 0.01 and P< or = 0.001) for all the various pairs of relatives, except between spouses. In addition, variance component analysis showed no significant household common environment contribution to variability of this trait, while the genetic contribution accounted for 60.6% regardless of the 4 classes of relatives. Taking the three polymorphisms into account did not modify the variance components. These results show that plasma VEGF concentrations are under genetic control in healthy families and that none of the 3 candidate polymorphisms significantly altered heritability.