Adolescents had lower rates of remission induction and shorter event-free survival than younger children in this study of consecutively treated patients with acute lymphoblastic leukemia (ALL). When compared to the younger patients (ages 1-9 years; n = 995), adolescents (ages 10-21 years; n = 338) were significantly more likely to have adverse prognostic features, including T cell phenotype, L2 blast cell morphology, higher serum lactate dehydrogenase level, higher leukocyte count, leukemic cell DNA index less than 1.16, and ploidy other than hyperdiploidy greater than 50. Within the adolescent group, outcome was worse for those older than 15 years. The increased frequency of unfavorable clinical and biologic features undoubtedly accounts in part for the poorer prognosis of adolescents with ALL. However, the independent prognostic significance of age greater than or equal to 10 years suggests that as yet unknown factors contribute to treatment failure in adolescent patients.