Bronchial responsiveness (BR) was assessed by the methacholine challenge test in 1,694 subjects from a sample of the general population (aged 8 to 73 yr) enrolled in a prospective epidemiologic study on the natural history of chronic obstructive pulmonary disease (COPD). Information on respiratory symptoms and risk factors for COPD were obtained with a standardized questionnaire. The provocative dose causing a 10%, 15%, and 20% decrease in FEV1 was reached in 939 (55%), 658 (39%), and 447 (26%) subjects, respectively, after the last cumulative dose of methacholine (i.e., 4.8 mg). The slope of the dose-response curve was also computed in order to attribute a parameter to subjects who did not reach the provocative dose. After natural log transformation, the slope (Ln Slope) of the curve showed a significant association with the degree of airway obstruction, as assessed by FEV1% predicted, FEV1/VC%, and FEV1/FVC%. Therefore, relationships between BR, sex, age, and smoking were evaluated after adjustments for the initial airway caliber (FEV1, FEV1 adjusted for height, and FEV1/VC%). Females showed significantly higher values of Ln Slope than did males after adjustments were made for baseline lung function. In males, higher BR was observed in childhood-adolescence age groups and at older ages, while in females a higher level of BR was observed during childhood. Significantly higher Ln Slope values were found for females who currently smoked than for non- and ex-smokers. No difference was observed in males in relation to smoking habit. (ABSTRACT TRUNCATED AT 250 WORDS)