Cotinine, the proximate metabolite of nicotine, has been identified as an indicator of smoke constituent exposure. Higher cotinine levels in African American cigarette smokers have been identified. Because African Americans experience disproportionate smoking-related morbidity and mortality, it is important to examine potential factors influencing these higher levels of cotinine. The current study examined selected factors of ethnicity, menthol cigarette preference, body composition and alcohol-use history on cotinine half-life in 6 days of smoking abstinence in African American and Caucasian women. A 7-day inpatient protocol was conducted in the General Clinical Research Center, in which day 1 was ad lib smoking and days 2-7 were smoking abstinence (n = 32). Plasma cotinine was measured every 8 h throughout. Average cotinine half-life was 21.3 h, similar to previously reported 18-20 h. Three women exhibited >14 ng/ml cotinine after 136 h of smoking abstinence. Host factors explaining 52.0% of variance in cotinine half-life and associated with longer half-life were being an African American menthol smoker, fewer years of alcohol use and greater lean body mass. Among menthol smokers, baseline cotinine level and cotinine half-life were not significantly different in Caucasian and African American women. Intra-individual cotinine half-life variation and CYP2A6 genotype were examined in substudies. To improve accuracy in correctly classifying non-smokers with cotinine levels, a period of at least 7 days of smoking abstinence may be warranted.