Only a few reports of zidovudine (ZDV) overdose have been described in the literature [1–4]. All cases occurred in HIV-1-infected patients, including one child [1]. Patients presented with nausea or vomiting, neurologic symptoms (ataxia, lethargia, nystagmus, seizures), signs of bone marrow toxicity (anemia, leukopenia, thrombocytopenia), or an increase in liver enzymes [1–4]. Clinical and haematological abnormalities were temporary in all cases. No case of ZDV overdose has been described among uninfected children born to HIV-1-infected mothers. ZDV prophylaxis administered antepartum and intrapartum to the mother and postpartum to the newborn for 6 weeks reduces perinatal HIV-1 transmission by approximately two-thirds [5]. Adding other prevention strategies, such as a combined antiretroviral therapy, bottle-feeding and elective caesarean delivery, the transmission rate is now estimated to be 1–2% in developed countries [5]. Therefore, exposed infants are treated with a 6-week course of oral ZDV (2 mg/kg, corresponding to 0.2 ml/kg of ZDV syrup, every 6 h). We report four cases of ZDV overdose occurring in healthy, uninfected children born to HIV-1-infected mothers. All mothers had been followed-up during pregnancy. They were given an appropriate antiretroviral regimen, containing ZDV during pregnancy, received intrapartum ZDV, and bottle-fed their infants. Three women underwent a caesarean delivery. All children were prescribed oral ZDV at discharge. In all cases, the mothers erroneously administered a ZDV amount ten-fold higher than the recommended dosage. This error, due to a misplaced or misread decimal point, is referred to as the ‘ten-fold’ error, is quite common in childhood, and may have disastrous consequences, including the child's death [6]. The AZT overdose was administered for 6–20 days (Table 1). Three children presented with variable clinical pictures that resolved. By contrast, the fourth child subsequently died due to a severe bacterial infection. In case 1, the incorrect administration was discovered at the first follow-up visit and only mild anaemia occurred. In case 2, the mother confirmed that she was giving ZDV at the first follow-up visit indicating the dose in mg, whereas she was administering the dose in ml. The error was discovered only when the child was hospitalized for sepsis due to Staphylococcus aureus infection and severe anaemia. Patient 3 was hospitalized at 10 days of age because of vomiting; lactic acidosis was noted. In case 4, the incorrect dosage was discovered at day 17, when the child was admitted to the hospital with seizures, neutropenia, anaemia, and septic status. A severe Streptococcus agalactiae meningo-encephalitis was diagnosed, which evolved dramatically, despite prompt antibiotic therapy, resulting in severe cerebral palsy, salt wasting syndrome, and hypothermia, which required maintenance of the child in an incubator for some months. Finally, she died at 8 months of age after ab ingestis pneumonia. Although the bacterial sepsis might have been coincidental, it was presumably facilitated by the ZDV-induced neutropenia.Table 1: Summary of four paediatric cases of zidovudine overdose.These inter-individual differences in response to similar ZDV overdoses might be influenced not only by total dose administered, but also by host characteristics. Intracellular ZDV concentrations are influenced by several individual factors, including thymidine kinase levels and the activity of some transmembrane drug transporters (multidrug resistance-associated proteins), which is genetically determined [7]. To date, the benefits of ZDV prophylaxis in infants exposed to prevent perinatal HIV-1 infection largely outweigh its adverse effects [5,8]. Nevertheless, cases of perinatal HIV transmission still occur in developed countries, mainly because of a failure to administrate an appropriate prophylaxis to the mothers and/or their infants, particularly to female drug addicts or immigrants [9]. Given the language difficulties and cultural differences, the latter may have limited access to healthcare services or even delay medical care [9]. Our report further highlights the risk of misunderstanding the medical prescriptions in certain women. Implementing adequate HIV education and counselling programs, improving physician–parent communication, taking greater care of the foreign families, and an intensive follow-up might all help to avoid misunderstandings in women who at are risk.