Children with acute lymphocytic leukemia (ALL) in remission and undergoing either chemotherapy or immunotherapy were tested for general cell-mediated immunocompetence and cell-mediated reactivity to tumor-associated antigens (TAA) using the following parameters: skin tests with recall antigens and extracts of lymphoblastoid cell lines; primary sensitization to dinitrofluorobenzene and picryl chloride; in vitro tranformation by mitogens and PPD; and lymphocyte-mediated cytotoxicity against a lymphoblastoid cell line and a panel of cryopreserved leukemic blasts. Reactivity in all assays of children on continuous chemotherapy was significantly depressed compared to similar patients later in the study. Patients on intermittent chemotherapy demonstrated much less immunodepression. The groups tested early during immunotherapy with BCG and allogeneic leukemic blasts were hyper-responsive (compared to published data) to primary sensitization with picryl chloride. Skin test reactivity to recall antigens and to tumor-derived lymphoblastoid cell lines was suppressed (as analyzed serial comparison) in this hyperimmunized group, possibly due to antigenic competition, and reactivity in all other assays was normal. The patients tested after 2-8 years of immunotherapy showed significantly higher positive skin-test responses to extracts of tumor-derived lymphoblastoid cell lines as compared to the other groups. The results of this multiphasic screen support the known effects of chemotherapy on immunocompetence. Moreover, they document the prompt return of immunocompetence with intermittent chemotherapy and during immuno-therapy. These results do not, however, indicate a striking augmentation of the immune response during immunotherapy as measured by these parameters.