In a multinational, population-based study from the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), 2648 children below 15 y of age were diagnosed with acute lymphoblastic leukaemia (ALL) in the years 1981-1996. The annual incidence was 3.9/100000 children and was stable throughout the study period. The development from regional or national protocols to common Nordic treatment protocols for all risk groups was completed in 1992 through a successive intensification of therapy, based on multidrug chemotherapy including pulses of methotrexate in high doses and avoidance of cranial irradiation in most children. For children with non-B-cell ALL (n=2602), the event-free survival (p-EFS) increased from 0.53+/-0.02 (diagnosed 7/81-6/86) to 0.67+/-0.02 (7/86-12/91) to 0.78+/-0.02 (1/92-12/96). The corresponding p-EFS values at 5 y were 0.57, 0.70 and 0.78, respectively. The main improvements were seen in the group of children with non-high risk leukaemia, with 5-y p-EFS values increasing from 0.60 to 0.76 and 0.85 for the three periods. In high-risk patients, progress has been moderate, especially in children with high white blood cell values at diagnosis. During the last 5-y period, only 10% of the patients received cranial irradiation in first remission while 90% of the patients received high doses of cytostatic infusions (methotrexate isolated or combined with cytarabinoside) and multiple intrathecal injections of methotrexate as CNS-adjusted treatment without any indication of an increased CNS relapse rate.