Three previous genetic association studies conducted in Korea and China investigated the relationship between IL3 single nucleotide polymorphism (SNP) rs40401 and asthma, but their results were inconsistent. We examined this relationship and the possibility of an interaction between IL3 SNP rs40401 and smoking in young adult Japanese women. Included were 89 women who met the criteria of the European Community Respiratory Health Survey (ECRHS) for asthma. Control subjects were 700 women without asthma according to the ECRHS criteria who had not been diagnosed with asthma and/or allergic rhinitis by a doctor and/or who had not met the criteria of the International Study of Asthma and Allergies in Childhood for rhinoconjunctivitis. A significant positive association was found between SNP rs40401 and the risk of asthma, with the TT genotype as the reference under the additive model: the adjusted odds ratio was 1.39 (95% CI: 1.004-1.93). The positive association was not statistically significant in any other genetic model. Compared with subjects with the TT or TC genotype of SNP rs40401 who had never smoked, those with the CC genotype who had ever smoked had a significantly increased risk of asthma: the adjusted OR was 2.67 (95% CI: 1.23-5.79); the additive interaction, but not the multiplicative interaction, was significant. This study suggests that IL3 SNP rs40401 is significantly associated with the risk of asthma in young adult Japanese women and reveals that the combination of ever smoking and having the CC genotype of IL3 SNP rs40401 is significantly positively associated with asthma.