Indirect, biochemical measures of cigarette use are valuable in confirming smoking status in both cross-sectional and cessation studies. This study compares two such biochemical markers, expired-air carbon monoxide (CO) and plasma thiocyanate (SCN), in a representative population sample of 2,237 adults (ages 18-74) from the baseline survey of the Stanford Five City Project. CO and SCN are both significantly higher in self-reported smokers than in nonsmokers and correlate well with number of cigarettes smoked per day. CO appears to be more sensitive and specific than SCN in comparison to self-report, and CO misclassifies a significantly smaller number of nonsmokers, regular smokers, and light smokers (less than 9 cigarettes per day) than does SCN. Together, CO and SCN better classify smokers and nonsmokers than do either alone. Neither biochemical is a reliable indicator in irregular smokers (no cigarettes in past 48 hr). Despite its much shorter metabolic half-life, CO is a better indicator of cigarette use than is SCN in this cross-sectional study. CO is generally simpler and less expensive to measure than is SCN, and CO may be a preferable indirect measure of smoking status in some studies of smoking cessation.