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In general, 70% of patients with psoriasis prefer topical therapy as the treatment of choice.To evaluate the efficacy and tolerability of 1% topical methotrexate gel vs. placebo (vaseline ointment) as treatment for psoriasis.Forty patients (20 females and 20 males) with chronic plaque-type psoriasis joined the study. Each patient was allocated to apply 1% methotrexate gel and placebo topically to their two target lesions, equal in area and disease severity, twice daily for 8 weeks. Lesions were scored at baseline and after 2, 4, 6, and 8 weeks of treatment for erythema, scale, and infiltration. The global improvement and histopathologic features were also assessed after methotrexate treatment.At the end of treatment, erythema was cleared totally in 47.5% of patients treated with methotrexate vs. 7.5% of those treated with placebo, and infiltration in 22% of patients treated with methotrexate vs. 2.5% of those treated with placebo (P < 0.01). Clinical improvement was almost the same for the two groups with regard to scale (P < 0.5). The global improvement was 97% for patients treated with methotrexate vs. 60% for those treated with placebo, and a significant difference was found between the groups (P < 0.01). Histopathologic improvement was achieved in the methotrexate group (P < 0.01). No side-effects were observed.The findings of this study suggest that methotrexate 1% in a hydrophilic gel is well tolerated and significantly more effective than placebo as a topical medication for the treatment of psoriasis vulgaris.