the hypothesis that the CYP2A6*12 allele might be equivalent to the two null alleles, *4 and *2 in respect to nicotine metabolism. ANOVA analysis provided no evidence of a difference between heterozygotes (excluding the three above-mentioned subjects) for the CYP2A6*12, *4 and *2 alleles (df=2, p=0.49), further evidence that CYP2A6*12 is a potential null allele. The two carriers for the novel amino-acid change, Y351H, display slow (*1H/*1D, 74%, compare to Table 3) and exceptionally slow (*12/*1D, 44%) metabolism respectively, also consistent with the amino acid change damaging enzyme efficiency, and the polymorphism occurring on the *1D rather than the *12 background.