To ascertain whether cessation of smoke exposure would decrease small-airway secretory-cell metaplasia, guinea pigs were exposed to daily cigarette smoke using a nose-only exposure system for 4 and 8 mo; an additional group was exposed to smoke for 4 mo and then air recovery for 4 mo ("ex-smokers"). Numbers of secretory cells per millimeter of basement membrane were calculated for each bronchiole from measurements of histologic sections stained with Alcian blue/periodic acid Schiff, and cumulative histograms were constructed. Smoke exposure was associated with a significant increase in numbers of secretory cells at 4 mo and 8 mo, although there was no increase in numbers beyond the 4-mo exposure period. In the ex-smoking group, secretory cells were reduced compared to the 4- or 8-mo smoking group, but continued to be greater than controls. We conclude that, in a guinea pig model, smoking produces secretory-cell metaplasia in the airways and that smoking cessation allows partial recovery of normal structure.