Between 1972 and 1975 the Children's Cancer Study Group conducted two clinical trials for the treatment of newly diagnosed patients with acute lymphoblastic leukemia. Upon achieving 3 yr of continuous complete remission, 316 children and young adults were randomly allocated either to discontinue chemotherapy or to continue chemotherapy for an additional 24 mo. With a median follow-up from the time of randomization of 50 mo, those patients who received 3 yr of therapy have demonstrated a statistically non-significant yet higher incidence of bone marrow relapse as compared to those patients treated for 5 yr (p = 0.09). However, the proportion of patients surviving 5 yr from randomization is 93% for the 3-yr treatment group and 89% for the 5-yr treatment group (p = 0.27). No significant difference was observed between the randomized groups for the occurrence of testicular relapse (p = 0.12), central nervous system relapse (p = 0.17), or first occurrence of relapse or death (p = 0.24). The relapse-free survival of patients treated for 5 yr as compared to those treated for 3 yr was not significantly higher in males (81% versus 75%, p = 0.14) or females (89% versus 89%, p = 0.95). This randomized study did not demonstrate a significant difference between treatment for either 3 or 5 yr.