Background The relation of IL17 polymorphisms to psoriasis risk and response to methotrexate has not been previously studied in Egyptians. Objectives To study the relation of IL17A (rs2275913 G>A) and IL17F (rs2397084 T>C) polymorphisms to psoriasis risk and assess their predictive role as regards response to methotrexate.Patients & Methods IL17A (rs 2275913) and IL17F (rs 2397084) polymorphisms were evaluated in 100 healthy subjects and 100 patients with chronic plaque psoriasis by real time-PCR. Patients were given methotrexate weekly intramuscularly (0.6mg/kg) for 12 weeks. Results IL17F TT genotype was more frequent in patients (87%) than controls (68%), while TC genotype was more frequent in controls (32%) than patients (13%). TT genotype was associated with increased risk of psoriasis whereas the TC allele was associated with a decreased risk. There was no significant difference regarding IL17A GG, GA and AA genotype frequencies between patients and controls. PASI ≥75% was achieved in 22 patients (73.3%) with the TT genotype and 8 patients (26.7%) with TC genotype (p=0.019). Conclusion IL17F (rs2397084 T>C) TT genotype could be considered a susceptibility marker in Egyptian patients. Psoriatic patients with TT genotype and T allele of IL17F (rs2397084 T>C) are likely to show a better response to methotrexate.