Interethnic differences in cytochrome P450 polymorphism might be responsible, at least in part, for the variations in drug disposition between ethnic groups. Of the various CYP2C9 alleles, CYP2C9*2 and CYP2C9*3 have been reported to have altered catalytic activities compared to the wild-type CYP2C9*1. The present study is aimed at analysing the CYP2C9 polymorphism in a Mexican-American compared with a Spanish population. Differences between the two populations of healthy volunteers, Mexican-Americans (n=98 subjects) and Spaniards (n=102 subjects), regarding the CYP2C9 allele frequencies have been found. CYP2C9 genotypes among the studied Mexican-American population are in equilibrium. The 95% CI were, respectively, 0.81-0.90 for CYP2C9*1 (n=169), 0.05-0.13 for CYP2C9*2 (n=16) and 0.031-0.10 for CYP2C9*3 (n=11). CYP2C9*4, *5 and *6 were found in none of the studied subjects. The frequency of CYP2C9*2 was lower among Mexican-Americans compared to Spaniards (P<0.05). The obtained frequency of CYP2C9 alleles is compatible with the genomic assembly of the constitutive potential ethnic origin of this population, and supports the need of pharmacogenetic studies for optimizing the recommended drug dosages to Mexican-Americans.