In an attempt to improve treatment outcome high-dose methylprednisolone (HDMP, 20-30 mg/kg, once a day orally) was used instead of a conventional dose of steroid (2 mg/kg/d, in 3 divided doses) in children with acute lymphoblastic leukemia (ALL) with increased risk factors. HDMP combined with cytotoxic agents (vincristine and L-asparaginase) resulted in an improved complete remission rate (94%) in 48 newly diagnosed children with ALL compared to 81% in 86 historical controls receiving standard dose steroid combined with the same treatment regimen. The bone marrow relapse rate was lower in patients who received HDMP (31%) than in controls (56%). Treatment was discontinued in 56% of 48 patients receiving HDMP and in 35% of 86 controls. The difference was significant (p < 0.05). The 5-yr continuous complete remission rate was significantly greater in patients received HDMP compared with the control patients (60% vs. 43%, p < 0.05). HDMP treatment was well tolerated without significant adverse effects. Moreover, during induction therapy the duration of leukopenia (< 2 x 10(9)/L) was shorter in patients receiving HDMP. We conclude that HDMP combined with other antileukemic agents increased the CR rate and prolonged the duration of remission in children with ALL who had increased risk factors. However, the optimal dosage of HDMP and its role in maintenance therapy should be determined in future, randomized studies.