Polymorphisms in cytochrome P450 genes encoding enzymes of critical importance for drug metabolism have the highest genetic influence on interindividual variations in drug bioavailability. Human CYP2D6 enzyme is claimed to be polymorphically expressed among different ethnic groups. It has been suggested to account for a large part of the interindividual differences in drug metabolism and pharmacokinetics. In the current investigation, 100 healthy unrelated subjects living in Tabriz, Iran, were randomly selected. Genotyping was designed to determine the frequencies of five major and important alleles: CYP2D6*2, CYP2D6*4, CYP2D6*5, CYP2D6*10, and CYP2D6*17. After collecting venous blood samples, polymerase chain reaction-restriction fragment length polymorphism methodology was performed for detection of the alleles (except CYP2D6*5, which has been detected using an allele-specific polymerase chain reaction procedure). Finally, the obtained data were used to determine the allele frequencies. The frequencies for CYP2D6 alleles *2, *4, *5, and *10 were 32%, 12.5%, 3%, and 9%, respectively. CYP2D6*17 was completely absent in this study group. Poor metabolizer phenotype can be related to *4/*4 and *4/*5 genotypes with a total frequency of 4%. This is the first study of the CYP2D6 genetic polymorphism in an Iranian population. The frequencies of the studied alleles resulted in degrees of differences between this population and Orientals, Saudi Arabians, and Caucasians, while similarities to the reported results obtained from the studies among Mediterraneans and South Indians are noticeable.