The beta(2)-adrenergic receptor (beta(2)AR) is a transmembrane protein expressed by airway smooth muscle cells. In vitro studies have shown that polymorphisms at amino acid positions 16 and 27 alter receptor function. The aim of this study was to examine the associations between the beta ( 2 ) AR polymorphisms and risks of asthma, chronic obstructive pulmonary disease (COPD) and respiratory symptoms in a sample of adults. Participants were part of a cross-sectional population-based study of risk factors for respiratory disease. A total of 1,090 Caucasian participants completed a detailed respiratory questionnaire, spirometry, methacholine challenge and measurement of gas transfer. Genotyping for beta ( 2 ) AR polymorphisms at positions 16 and 27 was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method. Haplotype frequencies for the two polymorphisms were estimated using the E-M algorithm. We found the Arg16 homozygotes had an increased risk of COPD (OR 5.13; 95% CI 1.40,18.8), asthma (2.44; 1.12,5.31) and symptoms of wheeze (1.84; 1.02,3.35). The Gln27 homozygotes had an increased risk of asthma (2.08; 1.05,4.13) and bronchial hyperreactivity (BHR) (1.92; 1.07,3.46). The Arg16/Gln27 haplotype was associated with asthma (1.63; 1.12,2.38) and COPD (2.91; 1.42,5.94). The Arg16/Gln27 beta(2)AR haplotype is important in COPD, asthma and BHR, and may be associated with more severe respiratory symptoms in middle-aged and older adults.