Cell-mediated cytotoxicity is considered to play a major role in immune defense and in particular in the killing of virus-infected and neoplastic cells. It appears to have some interesting implications when considering the infectious risk of acute lymphoblastic leukemia (ALL) children during immunosuppressive chemotherapy and the role of self-defense against minimal residual disease. We have studied natural killer (NK) activity and lymphokine-activated killer (LAK) activity in children during and after treatment for ALL. We observed that peripheral blood mononuclear cells in 22 children undergoing maintenance chemotherapy displayed significantly depressed NK activity compared with normal controls even when the proportion of NK cells was normal. LAK activity was also considered in 43 ALL children during and after maintenance chemotherapy. We observed that LAK activity was persistently comparable with that of normal controls. It seems definite that NK activity impairment is transient and is completely restored in ALL children a few months after chemotherapy has been successfully completed. The evidence that LAK activity is not impaired in ALL children may have some implications in view of a possible immunomodulatory approach in the presence of refractory disease.