To describe the role of airways responsiveness in predicting incidence of wheeze in early adolescence and to examine the association between airways responsiveness and active asthma symptoms, children who had been tested for airways hyperresponsiveness were assessed prospectively. Of 770 children in the East Boston Childhood Respiratory Disease Cohort who were between 5 and 9 yr of age at time of entry into the study, 281 children received airways challenges during voluntary follow-up conducted between 1980 and 1986. Each subject presented a sequence of wheeze or asthma diagnosis reports along with a sequence of time-varying covariates, including airways challenge results and symptom and exposure information. A robust "pooled repeated observations" analog of the proportional hazard regression model was used to assess associations among risk factors and the probability of incident wheeze or active asthma. In the analysis of wheeze incidence, airways responsiveness (elicited via eucapnic hyperventilation with cold air or methacholine challenge) among those free of a history of wheeze at a given visit was found to be associated with a greater tendency to develop wheezing in the next visit (odds ratio [OR] = 3.91, 95% confidence interval [CI] = 1.21, 12.66), after controlling for a constellation of known risk factors. In the analysis of recurrent asthma episodes, airways responsiveness at a given visit was associated with a greater tendency to have an asthma diagnosis reported at the subsequent visit (OR = 4.2, 95% CI = 1.92, 9.23). For subjects presenting multiple airways responsiveness challenge studies, two successive positive airways responsiveness results were independently associated with a higher likelihood of recurrent asthma episodes. These results confirm the predictive importance of airways responsiveness in the natural history of the development and persistence of asthmatic symptoms.