15 cases of acute leukemia (AL) displaying a TdT+, HLA-DR+ phenotype were studied; surface immunoglobulins, T cell markers and the common acute lymphoblastic leukaemia (c-ALL) antigen were negative, as were peroxidase and non-specific esterase cytochemical reactions. All cases were extensively investigated by conventional immunofluorescence (IF) and immunoperoxidase (IP), with a panel of monoclonal antibodies (MoAb), using both light and electron microscopy, and for ultrastructural myeloperoxidase (MPO). 8 cases, which were OKB2+, BA1+, B4+, J5- and BA2- by IF, expressed the J5 antigen in IP. These cases were therefore re-classified as ALL with a weak expression of the C-ALL antigen. The other 7 cases showed an OKB2-, BA1-, B4+, BA2+ phenotype at IF and were also positive for 1 or more anti-myeloid MoAb. These features were confirmed by IP study. 4 patients also presented ultrastructural positivity to MPO. These cases were considered as proliferations of early precursor cells capable of expressing both myeloid and lymphoid features. This study, while demonstrating the heterogeneity of TdT+, HLA-DR+ AL, suggests that the cell origin of many cases may be defined by extensive immunotyping at both IF and IP level. The prognostic and therapeutic implications of these findings are discussed, also in view of the poor prognosis often observed in the more undifferentiated cases of AL.