In the past 22 years, 113 patients with severe psoriasis have been treated with low-dose methotrexate (MTX) in our department. The maximum weekly dosage was 15 mg (Weinstein schedule), the estimated mean cumulative dose was 4803 mg, and the estimated mean duration of therapy was 8 years and 11 months. In 81% of the patients, prolonged clearance or near clearance was achieved, indicating the potent and sustained potential of MTX in the treatment of both the pustular and erythematosquamous variants of psoriasis. Eighty-three patients (73%) had side-effects, most frequently abnormal liver function tests, nausea and gastric complaints. Apart from hair loss in seven patients, there were no mucocutaneous side-effects, probably because of the low-dose treatment schedule. In 71 patients MTX therapy was discontinued; in 33 patients because of side-effects. In 55 patients one or more liver biopsies were performed. Fibrosis was seen in seven of these patients (13%) and cirrhosis in two (4%). There was no relation between liver biopsy classification and cumulative dosage or duration of MTX therapy, nor was there any relation between liver histology and abnormal liver function tests. During this 22-year period, there were no deaths or life-threatening side-effects attributable to MTX treatment. We conclude that low-dose MTX (< or = 15 mg/week) is a relatively safe therapy for severe psoriasis, if patients are carefully selected beforehand, and regular monitoring for side-effects and drug interactions is performed during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)