By using hypoxanthine guanine phosphoribosyltransferase (hprt) gene alterations and chromosome aberrations as in vivo cellular markers, human T, NK, and B cells originating from a single stem cell have been successfully cloned from the peripheral blood of an atomic bomb survivor from Hiroshima. These mutant lymphocytes were selectively cloned, taking advantage of their resistance to a purine analogue, 6-thioguanine. The cloned lymphocytes possessed the same hprt gene alterations and the same chromosome aberration (20q-), but exhibited different surface or functional phenotypes and different rearrangements of TCR or Ig genes. The chromosome aberration patterns strongly suggested that the original stem cell initiated differentiation into each cell type after exposure to atomic bomb radiation. Since the person studied here was exposed to the bomb at 17 yr age, the results suggested that common stem cells exist in adults for at least T, NK, and B cells. The use of hprt gene alterations as specific cellular markers provides a novel method for identifying stem cells in the lymphocyte lineage and for studying lymphocyte differentiation in humans.