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Leukaemic cells from 542 patients under 21 years of age with a diagnosis of acute lymphoblastic leukaemia (ALL) were typed with immunological cell surface markers between June 1975 and December 1979; 379 of these patients entered into the trials up until December 1978 have been followed for more than 1 year. They were divided into four subgroups: common (c) ALL, T (thymic) ALL, 'null' (or 'unclassified') ALL and a rare lymphoma/leukaemia type B-ALL. A T-cell phenotype was found more frequently in boys and was usually but not invariably associated with a high white cell count at presentation. A mediastinal thymic mass was present in 53% of T-ALL patients but was not observed in any unequivocal not-T ALL. Clinical prognosis differed substantially between the three major phenotypic classes, remission induction rate and remission duration being lowest in T-ALL, better in 'null' ALL, and highest in cALL (P trend less than 0 . 0001; P = 0 . 0002 for comparison of cALL versus T-ALL). There was a much higher incidence of CNS involvement in the T-ALL group than in the cALL group or 'null' All group and although this was strongly correlated with WBC count it was also significantly associated with T-ALL independent of WBC count. Overall in this series and also within the major cALL subclass there is a strong correlation between high WBC count and poor clinical response (remission induction and duration). When the three major immunological subclasses are adjusted for WBC count the prognostic correlation of antigenic phenotype is reduced and statistically insignificant. It is suggested that immunological (and enzymatic) phenotype of ALL subclasses may not be an independent correlate of prognosis but nevertheless is linked to other cell differentiation features, especially growth rate and sites of clonal expansion (e.g. marrow versus thymus), which critically influence the size of the clonogenic leukaemic population and its associated evolutionary status with the respect to drug resistant mutants at the time of diagnosis and introduction of therapy.

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A non-specific acid alpha-naphthyl-acetate esterase activity was investigated in human lymphoid cell populations from tonsils, blood, thymus and in different leukaemias. Four patterns have emerged. (i) The vast majority of T lymphocytes (peripheral blood, tonsils) showed a localized, intense reaction product ("T-like"). (ii) A thymocyte subpopulation expressed faint, localized enzyme activity ("Thy-like) but the majority of thymocytes showed no esterase activity. Some cells from acute lymphoblastic leukaemias with thymocyte surface characteristics had a "Thy-like" appearance. (iii) Most B lymphocytes and cells from chronic lymphocytic leukaemias were esterase negative. No activity was seen in mitogen activated peripheral blood T and B lymphoblasts from peripheral blood and in leukaemic blasts from the common form of childhood acute "lymphoblastic" leukaemia. (iv) Myeloid cells, including peripheral blood monocytes, and blast cells from acute myeloblastic and chronic granulocytic leukaemias showed an intense, diffuse reaction product (M-like). It is concluded that the modified esterase technique is a convenient marker for small mature human T lymphocytes in tissue sections and smears. It may also be helpful in the differential diagnosis of acute lymphoblastic leukaemia with T characteristics, the common form of acute "lymphoblastic" leukaemia and acute myeloblastic leukaemia.