The effects of multiagent chemotherapy were evaluated in 36 patients with acute lymphoblastic leukemia in long-term remission. Decreased numbers of neutrophils, lymphocytes, T cells and T-cell subpopulations (T(M), T(G), T4 [helper] and T8 [suppressor]) were found. Additional abnormalities were reduced numbers of natural killer (NK) cells, assayed using the myeloid/erythroid K562 cell line, and impaired immunoglobulin production by pokeweek mitogen (PWM)-stimulated, cultured mononuclear cells. Patients tested a year after chemotherapy was stopped showed a return to normal levels of neutrophils, lymphocytes, T, T(M) and T(G) cells. NK cells and the T4 cells, however, remain low, whereas the T8 cell numbers return to normal, and the helper to suppressor cell ratio remains abnormal for about three years. In experiments on PWM-stimulated cocultured cells, immunoglobulin production was decreased and abnormal T-cells, defective suppressor cell immunoregulation and relatively normal B-cell function were detected. The abnormal findings were probably the result of the multiagent chemotherapy.