Biochemical validation of smoking status has long been considered essential, but recent reports have questioned its utility in certain kinds of field trials. We describe efforts to biochemically validate self-reports of smoking cessation from participants in four large-scale randomized trials in outpatient clinics, hospitals, worksites, and dental clinics. These studies included over 5,000 adult smokers who participated in the population-based low-intensity intervention evaluations. At a 1-year follow-up, 798 subjects reported no tobacco use. We attempted to verify these reports using saliva continine/carbon monoxide validation procedures. Overall, there was a moderately high nonparticipation rate (27%), a low disconfirmation rate (4%), and a high self-reported relapse rate (12%) in the interval between survey and biochemical validation. There were no differences between intervention and control conditions on any of the above variables. Longer durations of self-reported abstinence were strongly related to increased probability of biochemical confirmation. Differences in results across projects were related to how biochemical validation was conducted. These results, as well as statistical power considerations, raise questions about whether biochemical validation procedures are practical, informative, or cost-effective in such population-based, low-intensity intervention research.