Intensification of chemotherapeutic regimens has improved survival in childhood malignant disease. To characterize the impact of this intensified therapy on some aspects of the immune system, we have, in an unselected material of 220 children with malignant disease, investigated serum immunoglobulin levels and lymphocyte response at diagnosis and then subsequently during and up to 4 years after cessation of therapy. In leukemia and Hodgkin's disease, all immunoglobulin isotypes decreased during therapy. A profound depression of immunoglobulin M levels, lasting well after completion of therapy, was seen in all tumor types. The mitogenic response was attenuated in patients with leukemia at diagnosis but was rapidly restored after institution of therapy. Patients with solid tumors, particularly Hodgkin's disease, had a reduced mitogenic response during therapy. Thus these patients exhibit multiple immunological disturbances. The basis of the pronounced immunoglobulin M deficiency remains unclear.