The commonly held belief that adult onset wheezing illness is primarily nonatopic in nature suggests that the role of atopy in the pathophysiology of bronchial hyperresponsiveness (BHR) in adult onset wheeze may be minimal. This study examined risk factors for BHR (BHR: provocative dose causing a 20% fall in forced expiratory volume in one second PD20 < or =16.38 micromol methacholine) among 82 subjects with adult onset wheeze and among 191 subjects who had never wheezed. Subjects were identified from a cohort of subjects aged 39-45 yrs who were known to have had no childhood wheeze and who were involved in a 30 yr follow-up survey. Risk factors for BHR were examined among all subjects with BHR and among subjects with BHR stratified according to whether or not they had ever wheezed. The prevalence of BHR was 40% (33/82) among the subjects with adult onset wheeze and 11% (21/191) among the subjects who had never wheezed. Lower baseline lung function (odds ratio (OR) = 0.94; 95% confidence interval (CI) = 0.92-0.97 per unit forced expiratory volume (FEV1)% predicted) and atopy (OR = 7.23; CI = 2.53-20.64 for all three measures of atopic compared to nonatopic) were associated with BHR, while smoking and family history showed no statistically significant relation to BHR. This pattern was also apparent in analyses stratified by symptom status. A family history of atopy increased the risk that BHR was accompanied by wheezing symptoms (OR = 4.75; CI = 1.53-14.72 for more than one affected relative compared to no affected relatives). These findings suggest that atopy is associated with bronchial hyperresponsiveness in adults known to have had no childhood wheeze. A familial factor reflecting genetic influences and/or shared environmental factors may influence whether bronchial hyperresponsiveness is associated with symptoms.