The purpose of the study was to identify a unique immunophenotype of normal or Philadelphia chromosome positive (Ph+) CD34+ cells that might be used to purify normal CD34+ cells from chronic myelogenous leukemia (CML) patients. An immunophenotypical study of CD34+ bone marrow cells of 20 patients with CML at diagnosis and during hydroxyurea treatment, and 39 controls were performed. All patients were Ph+, two patients had variant translocations and three patients displayed cytogenetic signs of clonal evolution. The immature progenitor cell compartment (CD34+ HLA-DR- and CD34+ CD38- cells) was comparable. The CD34+ AC133+ progenitor cell compartment was decreased in CML patients. We found no difference for any of the adhesion molecules examined except for CD62L, where the percentage of CD34+ CD62L+ cells was decreased in CML patients. The number of myeloid progenitors (CD34+ CD33+) was increased at the expense of B-lymphoid progenitors (CD34+ CD10+ and CD34+ CD19+) in CML patients indicating that B-lymphopoiesis is inhibited in CML. The megakaryocytic (CD34+ CD61+) and erythroid (CD34+ CD71+) progenitors were increased in CML patients. The number of CD34+ CD7+ cells was also significantly increased (mean 25.3% vs. 4.9%). However, the level of CD7 expression was quite heterogeneous, and the patients could be separated into two populations according to CD7 expression (more or less than 20% CD7+ CD34+ cells). The Sokal and Hasford risk scores did not differ between CD34+ CD7- CML and CD34+ CD7+ CML, but all patients with signs of disease progression clustered in the CD34+ CD7+ population indicating that the level of CD7 expression on CD34+ cells may be of prognostic importance in CML.