The effects of interval treatment were evaluated in 10 psoriatic patients on long-term treatment with low-dose oral methotrexate (MTX). In all patients, the dosage of MTX had already been tapered off as much as possible. After interruption of MTX treatment, the clinical course and changes in laboratory parameters were evaluated. The mean MTX-free period was 17 weeks, and the mean reduction in cumulative MTX dose was 76 mg (p = 0.05). However, only 3 patients preferred interval treatment to a continuous schedule. During the first 3 weeks of discontinuation, a significant decrease in the serum transaminases was observed, indicating a direct toxic influence of MTX on the liver parenchym. We conclude that interruption of long-term MTX treatment leads to a substantial reduction of the cumulative MTX dose and reduces the hepatotoxic load of MTX. It is necessary to motivate patients on long-term MTX treatment for regular treatment interruptions to establish a further reduction in their cumulative MTX dose.