||This study aimed to investigate the impact of the CYP3A5 and ATP-binding cassette sub-family B member 1 (ABCB1) C3435T polymorphisms on the inter-individual variability of quetiapine pharmacokinetics in a Jordanian population. Quetiapine plasma concentrations were measured in 34 healthy Jordanian Arabic volunteers. Twenty blood samples were collected over a 24-hour period following the administration of a 25 mg immediate release tablet. The pharmacokinetic parameters were determined from the plasma concentration-time profiles using the WinNonlin® software. The CYP3A5 and ABCB1 C3435T genotypes were determined by polymerase chain reaction. With regard to the CYP3A5 polymorphism, the *3*3 genotype carriers showed consistently higher exposure index values in comparison to the non-carriers, with differences ranging from 1.34- to 1.6-fold. While, the TT genotype subjects displayed a trend toward lower exposure and higher disposition (up to 2.2-fold) indexes when compared to the CC genotype carriers. These results may provide useful data that clinicians can utilize to optimize the quetiapine dose administered to psychotic patients.