Toll-like receptor 4 (TLR4) is the transuding subunit of lipopolysaccharide receptor and an important intracellular signal pathway of the innate immune response. Published data about the relationship between TLR4 mutations and atopy/asthma are not consistent. This study was performed to detect two commonly reported Asp299Gly and Thr399Ile polymorphisms in TLR4 gene in Singaporean Chinese and their possible association with atopy-related phenotypes. A total of 117 unrelated Singapore residents were randomly selected for this study. Among them, atopy was evident in 66 subjects while 61 had allergic rhinitis. Twenty-one patients had concomitant asthma and 17 were atopic. In all subjects, neither the Asp299Gly nor Thr399Ile polymorphism was found by DNA sequencing. This discrepant result could be due to the ethnic variation of allelic distribution in TLR4 gene. Although it is still debatable whether there is any role of TLR4 polymorphisms on atopy-related phenotypes, one needs to develop an appropriate model to investigate the interactions between genetic variations and environmental factors that contribute to the complex traits in allergic diseases.