Low single-breath diffusing capacity (DL(CO)) values are associated with anatomic emphysema, but the predictors of longitudinal change in DL(CO) over many years are unknown. Study subjects were adult participants in the longitudinal Tucson Epidemiology Study of Obstructive Lung Disease who had at least one DL(CO) measurement during either of two surveys 8 yr apart (n = 543). Smoking status was determined at each examination (current, former, or never smoker). Quitters were defined as those currently smoking at the baseline DL(CO) examination (1982-1983) and self-reported as no longer smoking at the follow-up exam (1990-1991). The longitudinal DL(CO) data were analyzed using repeated measures analysis; because of missing observations this was done using a saturated random effects model. The results showed that males had higher levels of DL(CO) than females, current smokers had significantly lower levels of DL(CO) than never smokers, but there was no difference in their mean slopes over time. Smoking history, assessed using pack-years of smoking, was associated with reduced DL(CO) levels, independent of whether current or ex-smokers. Males and females demonstrated equivalent rates of decline in DL(CO) that accelerated with increasing age, and mean DL(CO) declines were associated with declines in FEV(1) between surveys.