Methotrexate (MTX) is an effective anti-psoriatic agent but there are major concerns about its long-term toxicity, in particular to the liver. Reported frequencies and recommendations for monitoring patients on MTX vary considerably. The aim of this study was to analyse the frequency and severity of MTX-associated adverse drug reactions (ADR) in patients with psoriasis and psoriatic arthritis. A retrospective analysis was performed of 104 psoriasis and psoriatic arthritis patients (60 male, 44 female) treated with MTX between October 1968 and October 1998. The severity of ADR was classified according to Common Toxicity Criteria (CTC). Acute ADR was defined as adverse effects within the first 90 days of MTX therapy. ADR seen later were classified as chronic. In 83 patients 165 ADR were noted within the beginning of MTX therapy. In five patients treatment was terminated because of ADR. During long-term therapy 23 patients received < or = 2000 mg MTX (group A); 81 received a cumulative dose greater than 2000 mg (group B). The total frequency of ADR in group B and the frequency of ADR CTC grade 3 or 4 in general was not significantly increased in group B (chi2 test; P = 0.468). Group B was characterised as follows: CTC grade 3 or 4 blood count changes led significantly more often to the termination of MTX (Fisher's exact test; P = 0.048), CNS side-effects (P = 0.016) and infections were more frequent (chi test; P<0.001). Liver changes and serum enzyme level increases were not significantly more frequent in group B. ADR are common in psoriasis patients on MTX therapy independent of the cumulative dose. In most cases they are temporary by nature and mild. Liver changes and serum enzyme level increases were not a major problem in our patients.