We evaluated factors that might influence the course of lung function after 2 to 21 yr of follow-up in 81 nonallergic patients with chronic air-flow obstruction (CAO) and considerable lung function impairment (initial forced expiratory volume in one second as a percentage of inspiratory slow vital capacity (FEV1 % VC) ranging from 40 to 55% and increasing less than 15% after the administration of the anticholinergic bronchodilator thiazinamium). A more favorable rate of change in FEV1 was associated with less pack-years of smoking, less nonspecific hyperreactivity, and a higher degree of reversibility of air-flow obstruction, when expressed as the increase in FEV1 as a percentage of the predicted minus prebronchodilator FEV1 value. Nonspecific hyperreactivity and reversibility of air-flow obstruction appeared to influence the decline in FEV1 independently of baseline value of FEV1, both in smokers and ex-smokers. The hypothesis is put forward that regular bronchodilating therapy may be able to prevent deterioration of lung function. However, the possibility that interval therapy may ultimately produce the same results cannot be excluded. It seems to be important to stop smoking, both for the sake of its negative influence on the course of FEV1 and for the fact that a beneficial influence of bronchodilating therapy may become even more apparent.