We documented changes in airflow obstruction and airway responsiveness to histamine after a period of 5 +/- 1 y in 40 subjects with mild to moderate asthma, 14 men and 26 women, aged 20-68 y (mean: 43.6 y). Asthma had to be stable at both evaluations. Each subject answered a respiratory questionnaire and expiratory flows and airway responsiveness to histamine were measured. No significant difference was found between the sub-groups based on atopic status and medication use for mean 5-y changes in FEV1 or PC20. However, although severity of asthma was similar in both groups, the number of subjects who significantly increased their FEV1 or PC20 at 5 y tended to be higher in the group using corticosteroids regularly (> 9 months/y): FEV1: 35.7%, PC20: 42.9% compared to those using them intermittently (< 3 months/y): FEV1: 23.3%, PC20: 35.3% (p > 0.05). This difference was related to recent (< 6 months) use of inhaled corticosteroids. On the other hand, the number of subjects with a significant reduction in FEV1 or PC20 after 5 y was lower when inhaled corticosteroids were used regularly: FEV1: 14.3%; PC20: 28.6%, compared to intermittently: FEV1: 41.2%; PC20: 41.2%, although this difference was not statistically significant. Changes in FEV1 or PC20 at 5 y were not correlated with the duration of asthma, the number of months on inhaled corticosteroids, or age at the time of diagnosis. Airway responsiveness was most often improved in atopics compared to non-atopics. In conclusion, overall 5-y changes in FEV1 or PC20 in our group of subjects were minimally influenced by the duration of the asthma and age at the time of diagnosis. The number of subjects with improved airway responsiveness was higher among atopics and after regular use of inhaled corticosteroids. Further prospective studies should be done on the long-term influence of regular vs. intermittent use of inhaled corticosteroids on the natural history of asthma.