Human CHRNA3 and CHRNA5 are physically linked and partially overlap tail-to-tail [28]. We targeted a 26-kb region spanning exon 5 of CHRNA5 to exon 4 of CHRNA3 and sequenced 10 cases and 12 controls of European descent. The goal was to identify novel variants, genotype them in the larger sample, and test them for association with nicotine dependence.