Between January 1978 and August 1999, 29 infants with newly diagnosed acute lymphoblastic leukemia (ALL) were treated on three consecutive protocols. Eighteen patients with infant ALL diagnosed between 1978-1991 were included in Group 1. In this group, treatment comprised a two- or three-drug induction with prednisolone, vincristine and L-asparaginase, and maintenance therapy consisted of weekly oral administration of mercaptopurine and methotrexate for three years. Group 2: Between 1991 and 1999, 11 infants with ALL were treated by St. Jude Total Therapy XI (n=4) and XIII (n=7) protocols with minor modification. Three years' event-free survival (+/-SE) was 14 +/- 9% in group 1. In group 2, this rate was 25 +/- 22% in Total XI and 57 +/- 19% in Total XIII. Outcome for infants on protocols Total Therapy XI and XIII improved compared with that of group 1.