The present study investigated the outcome of asthma in a population of 181 adult patients 13 to 44 yr of age (median, 24 yr) who were extensively tested between 1962 and 1970 and in whom asthma was diagnosed. When retested 25 yr later, 38 subjects (21%) did not show bronchial hyperresponsiveness (BHR)(PC20 > 16 mg/ml), 45 subjects (25%) showed a FEV1 > 90% predicted, and 72 subjects (40%) did not report pulmonary symptoms. When absence of asthma was defined as no BHR, FEV1 > 90% predicted, and the absence of pulmonary symptoms reported by the patient, 20 subjects (11%) were no longer considered asthmatic when retested. Absence of asthma after 25 yr was associated with a younger age and less severe airway obstruction at first testing, odds ratios (OR) being 0.36 for age/10 yr, and 1.42 for FEV1/height2 (dl/m2). Absence of BHR was associated with a younger age, a higher FEV1, and a shorter untreated period (years between onset of asthma symptoms and specialized treatment of the disease) at first testing, and a lower total serum IgE level (IU/L) at second testing (OR, 0.48 for age/10 yr; OR, 1.37 for FEV1/height2; OR, 0.93 for untreated period; OR, 0.33 for log [IgE]). Neither sex nor atopy (one or more positive skin tests) were significant determinants of the outcome of both asthma and BHR. Our results suggest that in a substantial proportion of symptomatic asthmatics the disease improved, and that subsets may outgrow their asthma, even in adulthood. The data lend indirect support to the hypothesis that milder disease and earlier intervention are important for a beneficial outcome of asthma.