Studies of nicotine replacement by 2 mg nicotine polacrilex gum (NG) have typically found that one half to one third of plasma nicotine in recent smokers is replaced. This 5-year study sought to find the extent of nicotine replacement among ex-smokers in the longer term and to identify a mechanism for this relationship. The sample was the special intervention group (N = 3923) in the Lung Health Study, a controlled clinical trial involving smoking cessation. The extent of nicotine replacement was assessed by levels of salivary cotinine. Cotinine levels of ex-smokers using NG after 1 year (219 +/- 149 ng/ml) were similar to those in continuing smokers (290 +/- 159 ng/ml). After 5 years, cotinine levels were the same for NG-using ex-smokers (316 +/- 276 ng/ml), NG-using smokers (309 +/- 240 ng/ml), and NG-non-using smokers (311 +/- 198 ng/ml). Salivary cotinine among NG users at 1 year was only weakly correlated with baseline cotinine levels prior to smoking cessation. Although NG users appear to re-establish cotinine levels characteristic of their smoking, the mechanism by which this occurs remains unclear.