Background IL-16 is an immunomodulatory cytokine whose expression is increased in the bronchial mucosa, bronchoalveolar lavage fluid and induced sputum of asthmatic patients. It has been suggested that IL-16 has a regulatory role in the pathophysiology of asthma. A single-nucleotide polymorphism (T-295C) has been described in the promoter region of the gene and it has been hypothesized that this polymorphism may be associated with altered levels of IL-16 expression, and account for the increased levels of IL-16 seen in the asthmatic airway.Objective To determine the association between the T-295C promoter polymorphism and asthma, disease severity and atopy in a large Australian Caucasian population.Methods We used PCR and restriction fragment length polymorphism analysis to establish the allele frequency of the T-295C promoter polymorphism in a random Australian Caucasian population (n=176) and to characterize the polymorphism in a large Australian Caucasian population of mild (n=273), moderate (n=230) and severe (n=77) asthmatic patients, and non-asthmatic controls (n=455). Genotype association analyses were performed using chi(2) tests.Results The polymorphic C allele was present in 19% of the asthmatic population and 21% of the non-asthmatic population. There was no association between the polymorphism and asthma (P=0.153) nor with asthma severity (P=0.417) or atopy (P=0.157) in this population.Conclusion Although it has been hypothesized that the T-295C promoter polymorphism may be associated with increased IL-16 gene expression, it is not associated with asthma, disease severity or atopy in this Australian population.