Vascular endothelial growth factor (VEGF) is an angiogenic factor implicated in asthma severity. The objective of the present study was to determine whether VEGF single nucleotide polymorphisms (SNPs) are associated with asthma, lung function and airway responsiveness. The present authors analysed 10 SNPs in 458 white families in the Childhood Asthma Management Program (CAMP). Tests of association with asthma, lung function and airway responsiveness were performed using PBAT software (Golden Helix, Inc. Bozeman, MT, USA; available at www.goldenhelix.com). Family and population-based, revpeated measures analysis of airflow obstruction were conducted. Replication studies were performed in 412 asthmatic children and their parents from Costa Rica. Associations with asthma, lung function and airway responsiveness were observed in both cohorts. SNP rs833058 was associated with asthma in both cohorts. This SNP was also associated with increased airway responsiveness in both populations. An association of rs4711750 and its haplotype with forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) ratio in both cohorts was observed. Longitudinal analysis in CAMP confirmed an association of rs4711750 with FEV(1)/FVC decline over approximately 4.5 yrs of observation. VEGF polymorphisms are associated with childhood asthma, lung function and airway responsiveness in two populations, suggesting that VEGF polymorphisms influence asthma susceptibility, airflow obstruction and airways responsiveness.