Despite continuously more successful treatment of childhood acute lymphoblastic leukaemia (ALL), 2-5% of children still die of other causes than relapse. The Nordic Society of Paediatric Haematology and Oncology-ALL92 protocol included 1652 patients < or =15 years of age with precursor B- and T-cell ALL diagnosed between 1992 and 2001. Induction deaths and deaths in first complete remission (CR1) were included in the study. A total of 56 deaths (3%) were identified: 19 died during induction (1%) and 37 in CR1 (2%). Infection was the major cause of death in 38 cases. Five patients died of early death before initiation of cytotoxic therapy. Five patients died because of toxicity of inner organs and one of accidental procedure failures. Seven patients died of complications following allogenic haematopoietic stem cell transplantation (HSCT) in CR1. Girls were at higher risk of treatment-related death (TRD) [relative risk (RR) = 2.2; 95% confidence interval (CI(95%)): 1.2-4.0, P < 0.01], mostly because of infections. Risk of TRD was also higher in children with Down syndrome (RR = 4.5; CI(95%): 2.0-10.2, P < 0.00). In conclusion, 3% of children with ALL died of TRD, with bacterial infections as the most common cause of death. Girls and Down syndrome patients had a higher risk of TRD. Infections still remain a major challenge in childhood ALL.