Abstract5‐methoxypsoralen (5‐MOP) is considered an alternative to 8‐methoxypsoralen (8‐MOP) for photochemotherapy of psoriasis. We have compared the clinical efficacy and tolerability of 5‐MOP (1.2 mg/kg)‐UVA versus 8‐MOP (0.6 mg/kg)‐UVA therapy in 25 patients of skin type III and IV, affected by relapsing plaque‐type psoriasis of similar body involvement; indeed, the same patients were given 8‐MOP during 1 year and 5‐MOP during the subsequent year after relapsing. Both treatments cleared psoriatic lesions with a comparable number of exposures, but 5‐MOP required significantly higher cumulative UVA doses. The difference was due to the lower phototoxicity of 5‐MOP, as assessed by the determination of the minimal phototoxic dose, and to its higher tanning activity, as assessed by the weekly grading of pigmentation. Nevertheless, therapy by 5‐MOP‐UVA seemed particularly interesting in that it showed a higher tolerability since only 1 patient experienced nausea, whereas during therapy with 8‐MOP‐UVA nausea and/or vomiting occurred in 7 patients, sunburn in 6 and itching in 3. Since we have treated the same patients with the two drugs, our results were not influenced by interindividual variations of phototoxic responses, tanning ability and susceptibility to develop psoraleninduced short‐term side‐effects. It was concluded that, although long‐term side‐effects of the 5‐MOP‐UVA treatment have still to be determined, such treatment of psoriasis should be reappraised due to its higher tole