The aim of the proposed research was to investigate the role of UGTs,CYPs and ABCs transporter polymorphisms in interindividual variability of lamotrigine and valproate bioavailability. A total of 205 patients were enrolled, 131 treated with lamotrigine alone and 74 treated with lamotrigine and valproate. Determination of drug concentrations was performed by HPLC with diode array detector for lamotrigine and by immunoassay method for valproate. Genotyping of UGT2B7 -161C>T, UGT1A4 142T>G, UGT1A4 70C>A, ABCB1 1236C>T, ABCG2 421C>A, CYP2C9*2, CYP2C9*3, CYP2C19*2 i CYP2C19*17 was performed by real time PCR method, using TaqMan assays. Lamotrigine trough concentrations, adjusted for age, sex, body mass index, dose, were around 2.4-fold higher in patients co-treated with valproate. There was no overall effect of variant allele of UGT2B7 -161C>T, UGT1A4 142T>G, UGT1A4 70 C>A, ABCB1 1236C>T, CYP2C9*2, CYP2C9*3, CYP2C19*2 i CYP2C19*17 either on lamotrigine or valproate trough or trough/dose corrected concentrations. But there appeared a significant interaction between A-allele carriage in lamotrigine-valproate-treated subjects. ABCG2 421A-allele carriage (vs. CC) was associated with 61% higher lamotrigine trough (P=0.019), whereas in lamotrigine-only-treated subjects, A-allele carriage was associated with somewhat lower trough (vs. CC p=0.085) indicating a significant (P=0.004) two-fold difference in A-allele effect between treatment subsets. Valproate was associated with significantly higher lamotrigine troughs regardless of the ABCG2 genotype, but the effect appeared two-fold higher in ABCG2 421 A-allele carriers (GMR 4.29) than in 421CC-subjects (GMR 2.15).