Nonspecific airway hyperresponsiveness and atopy have been postulated to be risk factors that predispose individuals to the development of chronic obstructive pulmonary disease. The purpose of the present study was to examine the relationship of methacholine airway responsiveness and markers of atopy to rate of decline in lung function among 790 men, age 40 to 79 yr, followed in the Normative Aging Study. Airway responsiveness was assessed at the end of follow-up, which ranged from 14 to 24 yr. Multiple linear regression analysis indicated that greater methacholine airway responsiveness was associated with more rapid annual FEV1 decline. Stratified analysis suggested that this association was stronger among skin test-negative, current smokers. No significant relationship was found between serum IgE level and annual FEV1 decline. A weak but statistically significant correlation between eosinophil count and mean annual FEV1 decline was noted among skin test-negative individuals (r = -0.08; p = 0.03). Results from the present study do not show a clear association between atopy and decline in FEV1. These data, however, do indicate an independent association between heightened methacholine responsiveness on decline in FEV1 in adult males.