BACKGROUND The role of multidrug resistance 1 gene (MDR1 or ABCB1) polymorphism G2677T was studied in relation to paroxetine therapeutic efficacy and its side effects, as well as its association with selected demographic and clinical characteristics of patients with depressive disorder. MATERIAL AND METHODS To evaluate therapeutic efficacy, all patients (n=61) were rated at week 0, 2, 4, and 6 using the Hamilton Rating Scale for Depression (HAMD-21). They were labelled as "responders" (a decrease in HAMD ≥50%) and "nonresponders". The frequency of the side effects of nausea and sexual dysfunction were assessed using the Utvalg for Kliniske Undersogelser rating scale. The PCR-restriction fragment length polymorphism method was used for genotyping. RESULTS A significantly enhanced therapeutic efficacy of paroxetine was observed in patients carrying at least one T allele at week 4 (GG versus GT: 0.049; GG versus GT+TT: 0.035) and week 6 (GG versus TT: 0.001; GG versus GT+TT: 0.016; GG+GT versus TT: 0.003; G versus T: 0.001). On the other hand, carriers of the T allele showed only a nonsignificant increase in HAMD-21 score reduction. In the present study, no significant association between G2677T polymorphism and side effects was detected. However, we found a marginally significant difference between GG and GT genotypes regarding family history of depressive disorder (p=0.049). CONCLUSIONS Our study provided evidence for the potential effect of MDR1 G2677T polymorphism on paroxetine therapeutic efficacy, and eventually on depressive disorder family history. Larger multicenter studies and studies across other ethnic groups are needed to elucidate the contradictory implications of G2677T polymorphism with depressive disorder and its treatment.