Variability in response to drugs is a problem in clinical practice. The rate of patients who respond adequately to pharmacological therapy is generally around 60. The CYP450 multienzyme complex is a microsomal system located in the endoplasmic reticulum. The enzymes participate in phase I metabolism of xenobiotics. CYP3A4 is the isoenzyme mostly expressed in liver. Its gene is polymorphic, of which CYP3A4*1A is the wild allele and CYP3A4*2 is a polymorphism which consists of the S222P substitution in the amino acid sequence, affecting the activity of the enzyme. Methods: In this study, we determine the frequency of CYP3A4*2 polymorphism in Mexican individuals. 62 apparently healthy individuals, from Toluca de Lerdo, Mexico. The sample was 3 mL of peripheral blood. The DNA was extracted and PCR-RFLPs were performed. Results: 58 individuals possess the wild allele in homozygosity CYP3A4*1A/CYP3A4*1A (94%) and 4 individuals were heterozygous CYP3A4*1A/CYP3A4*2 (6%). The homozygous polymorphic CYP3A4*2/CYP3A4*2 was not found in any individual. Conclusion: The CYP3A4*2 polymorphism is rare in the population studied. Given the low frequency of CYP3A4*2 polymorphisms found in homozygous or heterozygous condition, it is advisable to consider the genotype of the patient before prescribing drugs metabolized by this gene.