American and Japanese overnight deprived tobacco smokers were compared with respect to expired CO, plasma nicotine and cotinine, and red cell carboxyhemoglobin. The participants were 51 of 59 American and 55 of 86 Japanese cigarette smokers of mixed gender who met similar strict criteria. Female and male American tobacco smokers were similar in mean age, number of cigarettes smoked per day, machine-rated nicotine and tar yield per cigarette and per 24 h plasma cotinine, calculated previous 24 h nicotine dose, and exhaled CO. Only mean plasma nicotine levels were significantly higher in American females. American and Japanese female smokers had similar tobacco uptake parameters. American and Japanese male smokers differed; the latter had higher plasma nicotine and lower cotinine levels as well as calculated 24 h dose of nicotine and lower exhaled CO. Japanese females and males were similar in all tobacco smoke uptake parameters. When the two racial groups were compared, irrespective of gender, the only statistically significant differences were lower mean exhaled CO levels and percent COHb in the Japanese. It is concluded that Japanese males inhale cigarettes in moderation compared to Americans. The results are discussed in relation to known ethnic, social, and genetic differences in CYP2A6 gene polymorphism.