A 1750 base pair cDNA to human terminal deoxynucleotidyl transferase (TdT) has been cloned. This cDNA detects a dominant 2200 base pair messenger RNA species in normal and leukemic cells synthesizing the enzyme. A quantitative dot blot assay was utilized to survey a number of clinical samples from patients with TdT positive and negative leukemias as well as cells from normal volunteers. A linear relationship was detected between the amount of TdT mRNA and the amount of enzyme activity in bone marrow cells. The assay is sensitive enough to detect normal TdT levels in bone marrow, and distinguish these levels from the lack of such mRNA in peripheral blood and bone marrow of patients with myeloid leukemia. Elevated levels of mRNA were found in two cases of patients in clinical remission. The prognostic significance of these observations must await further study.