Asthma is the most common chronic childhood disease in developed nations. Little is known about the relationship between airway responsiveness in infancy and the development of asthma later in life. The relationship of airway responsiveness at 1 mo with asthma, atopy, lower respiratory symptoms, and lung function at 6 yr of age was investigated prospectively in 95 white children from a randomly ascertained birth cohort. Baseline spirometry, airway responsiveness to histamine, and skin reactivity to common allergens were assessed at the age of 1 mo and 6 yr. Total serum immunoglobulin E (IgE) was measured from cord blood and at 6 yr. Blood eosinophil counts were measured at 6 yr only. Family, symptom, and exposure histories at both time points were derived from questionnaire data. Independently of the other factors assessed, increased airway responsiveness at 1 mo was significantly associated with the following parameters measured at six yr: decreased FEV(1) (p < 0.001); decreased FVC (p < 0.001); physician-diagnosed asthma (p < 0.001); and lower respiratory tract symptoms (p < 0.05). None of the other physiologic factors measured in infancy showed such consistent associations with important clinical and physiologic outcomes at age 6. These data suggest that airway responsiveness in early life defines a functional state that is associated with abnormal airway function, lower respiratory symptoms, and the emergence of asthma by 6 yr of age.