Increasing nonspecific airway responsiveness during aging may precede and predispose to the development of asthma in later life. Characteristics potentially related to longitudinal change in methacholine airway responsiveness were examined over a 3-yr follow-up interval among 435 middle-aged and older men. Initial and follow-up evaluation included spirometry, allergy skin testing with common aeroallergens, measurement of the serum concentration of total IgE, and blood cell counts (total leukocytes and eosinophils, basophils, and neutrophils as a percentage of total leukocytes). The initial values and annual rates of change of these characteristics were examined by multiple linear regression as potential predictors of annual change in methacholine dose-response slope. Annual change in basophil count was directly related to change in dose-response slope (p = 0.02). Initial values and annual rates of change of other cell counts, pulmonary function, allergy skin test reactivity, and serum total IgE concentration were not significantly related to change in dose-response slope. Cigarette smoking history was also not significantly related to longitudinal change in dose-response slope. These data suggest that inflammatory mechanisms involving the basophil may be important in the development of increasing nonspecific airway responsiveness during aging.