 Studies in our laboratory have shown that AAs metabolize nicotine, and to a greater extent, cotinine, more slowly than do whites 7,10 with slower metabolism by both the CYP2A6 and glucuronidation pathways. We have used the 3HCCOT ratio measured in blood or urine in several studies to show that CYP2A6 activity is lower in AAs compared to whites, including among children. More than 90 CYP2A6 gene variants have been identified. Although many are uncommon and their activity has not been determined 12, some are associated with large individual differences in the rate of nicotine metabolism 13. Studies of CYP2A6 genetics in AAs have only recently been reported. It is unclear whether reported gene variants in AAs can explain the substantial differences in nicotine and especially cotinine metabolism that we have observed in our prior studies. A comprehensive study of nicotine and cotinine kinetics and metabolism after IV dosing in relation to genotype, such as we have recently conducted in whites, is proposed to understand the metabolism of nicotine in AAs. 