CD34+DR- and CD34+DR+ cells were isolated from the marrow mononuclear cells of five patients with chronic myelogenous leukemia (CML) carrying the Philadelphia (Ph) chromosome. Analysis of bcr/abl hybrid mRNA in individual colonies from a single cell using reverse transcriptase polymerase chain reaction (RT-PCR) demonstrated the presence or absence of the hybrid mRNA. For patient 1 in the chronic phase of CML, the hybrid mRNA was detected in all colonies derived from CD34+DR+ and CD34+DR- hemopoietic progenitors. In contrast, for patient 2 in the chronic phase of CML, the mRNA was detected in all individual colonies from CD34+DR+ progenitors but not in any from CD34+DR- progenitors. For patient 3 in the chronic phase of CML, the mRNA was detected in all individual colonies from CD34+DR+ but in only some of the colonies from CD34+DR- progenitors. For patients 4 and 5 in the acute crisis of CML, the mRNA was found in a portion of colonies from CD34+DR+ and CD34+DR- progenitors. These results indicated that normal clones can persist in CD34+DR- progenitors in some patients with CML, even when chromosome analysis detects the Ph chromosome in all metaphases of bone marrow cells.