Thanks to a first grant from the European Union (Contract no. BMH4 983531 CA 1998/2001) PRINTO set up a randomized trial to compare intermediate versus higher doses of MTX in children with JIA. The trial was built on the current "standard of care" in such a way that the cost of insurance coverage, the medication, clinic visits, and laboratory monitoring, were paid by the usual method of cost reimbursement for clinical care in each participating country. The trial enrolled 633 patients from 20 different countries and showed that the plateau of efficacy of MTX in JIA is reached with the parenteral administration of 15 mg/m2/week and that further increase in dosage is not associated with any additional therapeutic benefit. MTX should be administered for up to 9-12 months to appreciate full therapeutic effect.