A 5-year prospective survey of 34 subjects with mild chronic bronchitis revealed marked individual variation in the annual rate of decrease in the forced expiratory volume in 1 sec. The mean annual decrease in the 1-sec forced expiratory volume was 0.046 +/- 0.057 liter. Although the annual decrease in the 1-sec forced expiratory volume was greater among smokers (0.056 +/- 0.061 liter per year) than non- and ex-smokers (0.016 +/- 0.021 liter per year; P less than 0.005), differences in tobacco consumption did not account for the individual variation. This variation was related, instead, to 3 phenomena believed to indicate the presence of host susceptibility to chronic bronchitis. These phenomena were bronchial reactivity to methacholine, ventilatory responsiveness to isoproterenol, and sputum eosinophilia. The correlation between the rate of decrease in 1-sec forced expiratory volume and the degree of methacholine reactivity was 0.76 (P less than 0.001); the correlation between the decrease in 1-sec forced expiratory volume and ventilatory responsoveness to isoproterenol was 0.45 (P less than 0.01). Deterioration of 1-sec forced expiratory volume was appreciably greater among those with sputum eosinophilia (0.062 +/- 0.06 liter per year) than among thse without eosinophilia (0.017 +/- 0.033 liter per year P less than 0.01). The progression of abnormality appeared to depend on an interaction between cigarette smoking and individual susceptibility. Even minimal tobacco consumption led to serious ventilatory deterioration when methacholine reactivity was high, whereas heavy smoking produced little effect on the decrease in 1-sec forced expiratory volume when methacholine reactivity was slight.