Genetic factors are important in defining total serum IgE levels. Linkage analyses have localized a gene or genes that influence atopic phenotype at chromosome 11q13. Variants of the FCER1B gene have been identified, which are associated with an increased risk of developing atopy and bronchial asthma. Given uncertain functional consequences and low frequencies of these coding variants of FCER1B, we screened for new mutations using 24 subjects with atopic asthma. A common -109C/T polymorphism at the promoter region of FCER1B was identified, although no variant was found in the entire coding region. We genotyped this promoter polymorphism in 226 healthy control subjects and 226 asthmatic subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Allele frequencies were 0.697 for -109T and 0.303 for -109C in 226 healthy control subjects. No significant difference in the distribution of -109C/T polymorphism was found between asthmatic subjects and healthy control subjects. A homozygosity for the -109T allele, however, was associated with increased total serum IgE levels in 226 subjects with asthma (p = 0.0015). The strongest evidence for an association between total serum IgE levels and -109C/T polymorphism (p = 0.0004) was obtained when age at onset of asthma was incorporated into the analysis. Our findings may represent genetic heterogeneity and complex interactions between genetic and environmental components involved in the regulation of total IgE levels, providing evidence that the -109C/T polymorphism of the FCER1B promoter region is one of the genetic factors identified thus far, which affects total serum IgE levels in a Japanese population.