Association and linkage studies of beta₂-adrenergic receptor (beta₂AR) polymorphisms in relation to the expression of asthmatic phenotypes and immune regulatory mechanisms have shown inconsistent results. This study was designed to analyze the relationship of particular combinations of single nucleotide polymorphisms (SNPs) or haplotypes of the beta₂AR gene with bronchial asthma, bronchodilator response, and total IgE. By direct DNA sequencing, five SNPs (in positions -47, -20, 46, 79, and 252) of beta₂AR gene were determined and combined with haplotypes in 201 asthmatic patients and 276 normal controls recruited from the Chinese Han population. Significantly higher bronchodilator response was observed in patients with homozygotic genotype 46A/A (13.40 ± 3.48%), compared with those with homo-46G/G (7.25 ± 3.11%) and heterozygotes 46A/G (7.39 ± 3.14%), respectively (p < 0.0001). There was also a significant difference in bronchodilator response when beta₂AR haplotypes were analyzed (p = 0.003). From two common SNPs at positions 46A/G and 79C/G, we had determined three haplotypes that constructed six haplotype pairs. Comparison of the mean delta forced expiratory volume in 1 second (FEV₁) values for the six haplotype pairs showed significant difference. Subjects homozygous for 46A/79C (Arg16/Gln27) had the highest deltaFEV₁ (13.40 ± 3.48%) and those with 46G/79C (Gly16/Gln27) homozygote had the lowest (6.43 ± 0.55%). The two SNP haplotype pairs were significantly associated with delta FEV₁ (p < 0.0001). Significantly higher total IgE levels were found in patients with homozygotic carriers of 79C genotypes (p = 0.022) and homozygotic haplotype -47 T/-20 T/46 A/79 C/252 G (p < 0.0001). These results indicate that the manifestation of asthma might be affected by either an individual beta₂AR SNPs or beta₂AR haplotype.