Background. Mercaptopurine (6-MP) and methotrexate (MTX) form the backbone of maintenance therapy for childhood acute lymphoblastic leukemia (ALL). It is widely noted that the inter- and intrapatient variations in the clinical efficacy and adverse effects of 6-MP and MTX are enormous, and optimal dosage varies considerably. The aim of this study was to elucidate the factors that affect the optimal dosage setting of 6-MP/MTX in the maintenance phase of treatment. Methods. Fifty children (aged 1 to 15) who were diagnosed as having ALL in our institution between April 1995 to March 2010 and who finished maintenance therapy were enrolled in this study. We investigated the 6-MP/MTX dosages from the beginning (6-MP/MTX: 40 mg/m² / 25 mg/m²) and compared patients' characteristics (sex, white blood cell count, age, immunophenotype, body surface area, prednisolone response, risk classification, obesity index) and relapse rates across each category. Results. Thirty-four patients needed to change their 6-MP dosage (increase, n=20; decrease, n=14), whereas 18 patients needed to change their MTX dosage (increase, n=3; decrease, n=15). The patients' characteristics were not significantly different in each category of dosage changes; on the other hand, it was shown that 4 of 7 relapse patients experienced an increase in 6-MP dosage of more than 50% within the first 6 months after the start of maintenance treatment. Conclusions. In this study, we conclude that the patients' characteristics are not related to the 6-MP/MTX dosage change in maintenance therapy, and it is suggested that the major increase in 6-MP dosage may predict the occurrence of relapse.