Many human cytochromes P450 (CYP) enzymes are polymorphically expressed, resulting in interindividual and interethnic differences in the metabolism of substrate drugs. Little is known about the genetic variation of CYP enzymes in Canadian Native Indians. We therefore determined the CYP2C19 and CYP2A6 mutant allele frequencies in 159 Canadian Native Indians and compared them with white and Asian subjects. Canadian Native Indians differed significantly from both white and Asian populations in allelic patterns of both CYP2C19 (19.1% CYP2C19*2 and 0% CYP2C19*3) and CYP2A6 (0.9% CYP2A6*2 and 13.9% CYP2A6*3). In addition, analysis of the Canadian Native Indian data suggested that there may be an association between the presence of the CYP2C19 and CYP2A6 mutant alleles such that the co-occurrence of these 2 alleles is higher than would be predicted on the basis of their individual frequencies in this population.