The aim of this study was to determine the distribution of peripheral blood T and B lymphocytes in children with ALL in remission, before and after cessation of 3 yr of immunosuppressive therapy. Immunofluorescence of viable cells and rosette formation were the two methods used to identify B and T cells, respectively. Though combination chemotherapy depresses the total lymphocyte population, B lymphocytes were more depressed than T lymphocytes. On the last day of therapy, the population of lymphocytes bearing IgG-M (B cells) was markedly reduced, but the percentage of RFL (T cells) was within normal values. After chemotherapy was stopped, and in the absence of extrinsic antigenic stimulation, there was an immunological rebound in the B cell compartment. During the first 3 months off therapy, there was an increase in intensity of fluorescence and in the proportion of IgG-M-bearing lymphocytes above the levels of normal controls. Assays of lymphocytes bearing IgG, IgM and IgA indicate that there was a rebound of IgG and IgM but not IgA lymphocytes. Changes in the proportion of RFL as a function of time off therapy were inversely proportional to those observed for IgG-M-bearing lymphocytes, that is, the percentage of RFL decreased during the first 3 months off therapy. When the absolute numbers of B and T cells were compared, it was found that B lymphocytes reached a plateau phase after 2–3 months off therapy, but T lymphocytes continued to rise beyond this period, reaching normal levels at 12+ months off therapy. These results provide evidence, at the single cell level, of the immunological rebound that occurs after cessation of therapy and suggest that the kinetics of recovery are different for T and B lymphocytes.