The radiobiological features of leukemic progenitor cells (LPC) freshly obtained from 14 T-lineage acute lymphoblastic leukemia (ALL) and 11 B-lineage ALL patients were evaluated using LPC colony assays. No significant radiobiological differences were observed between T-lineage versus B-lineage ALL LPC. Notably, the D0 values displayed a significant interpatient variation in both groups, indicating a pronounced heterogeneity in the radiation sensitivity of LPC. LPC from some patients were very radioresistant, and in additional experiments using cryopreserved bone marrow blasts, up to 32% of LPC could survive 1600 cGy delivered at 100 cGy/min. In six of 11 T-lineage ALL cases and five of ten B-lineage ALL cases, a distinct initial shoulder was present on the single dose radiation survival curves, providing circumstantial evidence that LPC are able to repair sublethal radiation damage. A greater proportion of LPC survived 400 cGy when the dose was delivered in two fractions instead of a single dose, providing direct evidence that LPC in ALL possess a substantial capacity to repair sublethal radiation damage. The interpatient differences in Dq and recovery factor values indicated a marked heterogeneity in the ability of LPC to repair sublethal radiation damage. Analysis of the dose rate effects on the radiation survival of LPC in four ALL cases suggested that the radiation sensitivity of LPC is dose rate dependent. Normal bone marrow progenitor cells (colony-forming unit, granulocyte-macrophage, and burst-forming unit, erythroid) were more radiosensitive and unable to repair sublethal radiation damage. To our knowledge, this report represents (a) the first detailed comparative analysis of the radiobiological features of freshly obtained LPC in T-lineage and B-lineage ALL patients, and (b) the first elucidation of radiobiological differences between leukemic ALL versus normal bone marrow progenitor cells.