The objective of this study was to determine if the weight gain that accompanies smoking cessation is independently associated with reductions in FEV1 and FVC, using a multicenter randomized intervention trial of smoking cessation in 10 communities in the United States and Canada. Enrollees were currently smoking women and men 35 to 60 yr of age with mild-to-moderate airway obstruction. Participants were randomized to one of three study groups: an intensive smoking cessation program with an inhaled bronchodilator (or a placebo), and usual care. Changes in absolute and percent predicted FEV1 and FVC between baseline and fifth annual follow-up visit were monitored in relation to changes in body weight during the interval. At the baseline examination, percent predicted FEV1 was maximal at 90 to 100% ideal body weight (IBW) and was lower as body weight deviated from this range. The FVC decreased linearly when IBW exceeded 100%. Weight gain was greatest during the first 12 mo after smoking cessation. Weight gain was associated with lower fifth-year FEV1 and FVC in all smoking categories: continuous smokers, intermittent smokers, and sustained quitters. The FVC was affected by weight gain more than was the FEV1, and the FEV1 was affected by smoking cessation more than FVC. Men showed more impairment of FVC with weight gain than did women, possibly because of differential patterns of fat deposition. In sustained quitters, after adjustment for baseline factors, the estimated reduction of FVC was 17.4 ml/kg weight gain for men and 10.6 ml/kg for women. The estimated loss of FEV1 was 11.1 ml/kg weight gain for men and 5.6 ml/kg for women. Lung function after smoking cessation is significantly influenced by weight gain and affects men more than women. The deleterious effects of weight gain are small, however, in comparison with the beneficial effects of smoking cessation.