Diabetes mellitus has been inconsistently associated with a reduced level of pulmonary function. To elucidate this association further, we analyzed the relationship of diabetes and of fasting blood glucose to the level of pulmonary function assessed by spirometry in the 3,254 members of the Framingham Offspring Cohort. Diabetes was defined as a fasting blood glucose of 126 mg/dl or more or pharmacologic treatment. Subjects were classified as current, former, or never smokers based on questionnaire responses. Predicted pulmonary function was determined from the coefficients of a regression of pulmonary function on age, sex, and body habitus in the 1,110 never smokers. Both the diagnosis of diabetes and a higher level of fasting blood glucose were associated with lower than predicted levels of pulmonary function. The adverse effect of diabetes and glycemic level on pulmonary function was stronger among ever smokers than never smokers, suggesting an interaction between the level of fasting glycemia and tobacco smoking.