<i>Background:</i> A role for neuronal modulation of inflammation and airway hyper-responsiveness has been well described in asthma, and neurotrophins provide the link between inflammation and neuronal dysfunction. Brain-derived neurotrophic factor (BDNF) is an important mediator in this interaction. The aim of this study was to analyze the possible relationship between polymorphisms of the gene encoding BDNF and susceptibility to asthma. <i>Methods:</i> 341 families with at least 2 siblings with asthma were genotyped for 4 <i>BDNF</i> polymorphisms (rs6265, rs2030324, rs988748 and rs7124442). <i>Results:</i> Analysis by family-based association tests revealed no significant association between any polymorphisms analyzed and asthma susceptibility. Furthermore, <i>BDNF</i> polymorphism was not associated with asthma-related phenotypes such as FEV₁ % predicted, bronchial hyper-responsiveness, IgE level, asthma and atopy severity scores. <i>Conclusions:</i> Our results suggest that genetic variation in the <i>BDNF</i> gene does not contribute significantly to asthma susceptibility or severity.