Variations in nicotine metabolism are thought to contribute to differences in cigarette consumption between African Americans and Caucasian adult smokers. To investigate the potential mechanism of previously documented lower smoking rates among African-American adolescent smokers seeking cessation treatment, we measured nicotine metabolite ratios as markers of the metabolic disposition of nicotine, which is generally considered to be under the influence of cytochrome P450 (CYP) 2A6. Plasma ratios of trans-3'-hydroxycotinine (3HC) to cotinine (COT) were examined in 92 cessation treatment-seeking adolescents (mean age 15.2 years, standard deviation [SD] 1.3, 69% female, 31% African American, mean Fagerström Test for Nicotine Dependence [FTND] 6.5, SD 1.6, mean years smoked 2.6, SD 1.6). Groups were similar in age, gender distribution, and mean FTND score. Analysis with independent t tests revealed significantly lower number of cigarettes per day (CPD) (15.1, SD 7.6 vs 19.6, SD 8.0, P=.013) and nicotine metabolite ratios (0.27, SD 0.15 vs 0.35, SD 0.16, P=.026) in African-American compared to Caucasian adolescent smokers. Consistent with metabolic variation, mean COT/CPD ratio was significantly higher in African-American compared to Caucasian adolescents. Results remained statistically significant when comparing menthol smokers by ethnicity. These findings are consistent with those found among adult smokers and provide a putative mechanism for reported ethnoracial differences in adolescent cigarette consumption. Our results underscore the need for measures independent of consumption for determining degree of nicotine dependence and treatment selection across ethnicities, even among youths.