We examined whether the allegedly aberrant expression of the lymphoid lineage associated DNA polymerase, terminal deoxynucleotidyl transferase (TdT), in acute myeloid leukaemia (AML) is associated with alterations of the enzyme at the cellular, biochemical or transcriptional level when compared to lymphoid leukaemia (ALL), either lacking or expressing myeloid antigens. By flowcytometric analysis, the intensity of TdT staining with monoclonal anti-TdT antibody was considerably weaker in TdT+ AML and myeloid+ ALL (M+ ALL) than in myeloid- ALL (M- ALL). TdT enzyme activity in TdT+ AML was on an average 10%, and in M+ ALL 25% of that measured in M- ALL. Anti-TdT antibodies precipitated a major specific protein of identical relative molecular mass (58 kD) from metabolically labelled TdT+ myeloblasts and lymphoblasts. By Northern blot analysis and ribonuclease protection assay, TdT transcript levels were significantly lower in TdT+ myeloblasts and M+ lymphoblasts than in M- ALL (P < 0.0001). The level of TdT transcription in AML was independent of the simultaneous expression of lymphoid-specific antigens, such as CD2 and CD19. Our data demonstrate that TdT expression is downregulated in association with myeloid features, not only in AML but also in ALL. This observation may provide the molecular basis for the differential therapeutic responsiveness, particularly to glucocorticoids, in these various leukaemia subtypes.