Antibody responses to two doses of a bivalent influenza vaccine containing A/Victoria/75 (A/Vic/75) and A/New Jersey /76 (A/NJ/76) viral antigens were studied in 22 children receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL), 16 children no longer receiving therapy for ALL, and 50 sibling controls. Before immunization, the three groups showed no difference in titer of antibody to either antigen. After the first immunization, children off therapy showed significantly higher titers to A/NJ /76 than did either sibling controls or children receiving therapy (P < 0.01). After the second immunization, children off therapy showed significantly higher antibody titers to both antigens than did children receiving therapy or controls (P < 0.01 for both A/NJ/76 and A/Vic/75). Antibody titers of children receiving therapy were not significantly different from those of controls. A year later, there were no significant differences in antibody titers among the groups. Thus, children with ALL who are receiving chemotherapy respond normally to two doses of influenza vaccine, whereas children off therapy manifest abnormally high titers of antibody to both influenza virus antigens.