Because of its involvement in the regulation of airway tone, the beta(2)-adrenoreceptor is considered a candidate for bronchial hyperresponsiveness (BHR) associated with asthma. This notion is supported by several reports that have implicated the chromosomal region 5q31-q33 harboring the gene for the beta(2)-adrenoreceptor in the genetics of asthma and related phenotypes. We performed a population-based association study focusing on BHR as a qualitative trait and omitting other asthma-related phenotypes. From a German population sample of 1,150 individuals we extracted all 152 bronchohyperreactive probands, who were compared with 295 bronchonormoreactive control subjects. All individuals were genotyped for three single nucleotide polymorphisms of the beta(2)-adrenoreceptor gene resulting in variants at the amino acid positions 16, 27, and 164. The genotyping protocol used allowed the determination of haplotypes of these polymorphisms. Whereas no individual polymorphism was associated with BHR, the Gly16/Gln27/Th164 haplotype was significantly underrepresented in the case group indicating a protective effect of this haplotype with regard to BHR. Upon reanalysis by sex a significant association persisted only for female probands.