We found that when marrow cells from four patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia were maintained in culture for two to four weeks, a previously undetectable population of chromosomally normal hematopoietic cells (including erythroid, granulopoietic, and pluripotent progenitors) became readily demonstrable in three cases. Time-course studies showed that in such cultures the dominant Philadelphia chromosome-positive population rapidly disappeared, in contrast to coexisting chromosomally normal progenitors, which remained detectable for periods of two to three months. Long-term marrow cultures thus offer a new approach to the assessment of a suppressed but functionally intact population of chromosomally normal hematopoietic stem cells in patients with chronic myelogenous leukemia.