The distribution of T, B and null lymphocytes was studied in the peripheral blood (PB) of 34 children with acute lymphocytic leukemia (ALL), at diagnosis and during the course of their disease. All patients received the same chemotherapy. At diagnosis, the proportion and absolute numbers of T lymphocytes fell into 2 groups, a "low" group (medians 8%, 318/mm3) and a "normal" group (medians 60%, 1405/mm3). Patients with a low proportion of T cells tended to have a high proportion and absolute number of null cells (correl. coeff. r = 0.94). This group has had high white blood cell counts (median = 29,600/mm3) and a high proportion of blasts (84%). During remission, the proportion of T cells returned toward normal (40-75%) in both groups. Four patients in the low T group relapsed; T cells again fell to low levels and returned to normal in response to new therapy. Three interpretations of these observations are suggested: 1) Active leukemia may cause normal lymphocytes (T cells and to a lesser degree B cells) to lose their surface markers; 2) Acute leukemia may inhibit maturation of normal lymphoid cells, and thus T or B markers are not sufficiently developed to be detectable; and 3) Cells without surface markers (null cells) may be a part of the malignant population, even though they are not morphologic blasts. Further studies are necessary to test these hypotheses.