Beta2-adrenergic receptor (beta2AR) gene polymorphisms have been reported to be associated with various asthma-related traits in different racial/ethnic populations. However, it is unknown whether beta2AR genetic variants are associated with asthma in African Americans. In this study, we have examined whether there is association between beta2AR genetic variants and asthma in African Americans. We have recruited 264 African American asthmatic subjects and 176 matched healthy controls participating in the Study of African Americans, Asthma, Genes and Environments (SAGE). We genotyped seven known and recently identified beta2AR SNP variants, then tested genotype and haplotype association of asthma-related traits with the beta2AR SNPs in our African American cohort with adjustment of confounding effect due to admixture background and environmental risk factors. We found a significant association of the SNP -47 (Arg-19Cys) polymorphism with DeltaFEF(25-75), a measure of bronchodilator drug responsiveness, in African American asthmatics after correction for multiple testing (P = 0.001). We did not observe association of the SNP +46 (Arg16Gly) variant with asthma disease diagnosis and asthma-related phenotypes. In contrast to previous results between the Arg16Gly variant and traits related to bronchodilator responsiveness, our results indicate that the Arg-19Cys polymorphism in beta upstream peptide may play an important role in bronchodilator drug responsiveness in African American subjects. Our findings highlight the importance of investigating genetic risk factors for asthma in different populations.