The physiopathology and significance of asymptomatic airway hyperresponsiveness (AHR) are still to be defined. Over a 3-yr period, we compared clinical, immunologic, and physiologic features of 30 subjects who had asymptomatic AHR with those of 30 symptomatic asthmatic subjects and 30 normoresponder subjects (age: 31.9 +/- 1.4 yr [mean +/- SEM]; n = 90). Each subject completed a respiratory questionnaire and underwent spirometry, measurement of bronchodilator response and peak expiratory flows, an allergy skin-prick test, blood eosinophil count, assay for total serum IgE level, and methacholine challenge. These tests were repeated annually, at the same period of the year, for 3 yr. Subjects with asymptomatic AHR had greater bronchodilator responses (p = 0.001), variability of peak expiratory flow rate (PEFR) (p = 0.02), and prevalence of atopy (p = 0.02) than did the normoreactive subjects. Compared with asthmatic subjects, subjects with asymptomatic AHR had a lower blood eosinophil count (p = 0.004), higher mean FEV1 (p = 0.006), and weaker bronchodilator response (p = 0.02), but an even greater perception of bronchoconstriction (p < 0.001). After 3 yr, the concentration of methacholine provoking a 20% decrease in FEV1 (PC20) had decreased significantly in the asymptomatic AHR subjects (p < 0.0001) as compared with the other two groups, and of the 28 subjects studied at this time, four (14.3%) had developed asthma symptoms. These last four subjects were atopic and exposed to animals when they developed asthma, had a familial history of asthma, and had an increased baseline AHR as compared with the subjects who did not develop symptoms. In conclusion, this study shows that over a 3-yr period, subjects with asymptomatic AHR had a greater increase in airway responsiveness and frequency of development of asthma symptoms than did normoresponsive subjects. Allergen exposure in sensitized subjects at the time of the study, and genetic predisposition, seemed the main risk factors for the development of symptomatic asthma in this population.