The hematopoietic system is controlled by growth factors (cytokines) which can influence cell survival, proliferation, differentiation and functional activation. The study of cytokine receptor expression by flow cytometry could allow us to differentiate between normal and tumoral cells. We analyzed the expression of the interleukin-3 (IL-3) receptor a chain (CD123) in 22 normal samples and in a wide panel of hematologic malignancies using flow cytometry. We found that CD123 was expressed in the myeloid progenitor subpopulation but in contrast, normal lymphoid progenitors lacked CD123. We analyzed the CD123 expression pattern in 64 patients with acute leukemia, 45 with acute myeloid leukemia (AML) and 19 with acute lymphocytic leukemia (ALL)(13 B-cell lineage ALL and 6 T-cell lineage ALL). All the AML cases except two patients with M7 and all the B-cell lineage ALL patients were CD123 positive. In contrast, all the T-cell lineage ALL cases tested were CD123 negative. We also studied the CD123 expression pattern in 122 patients with a B-cell chronic lymphoproliferative disease (B-CLPD). CD123 was positive in three situations: 1) typical cases of hairy cell leukemia showed a specific, strong CD123 expression, 2) a subgroup of atypical chronic lymphocytic leukemia with a marked CD11c expression was also CD123 positive, and finally 3) transformed B-CLPD showed the phenomenon of transition from CD123 negativity to CD123 positivity simultaneuosly with morphologic changes. In summary, our data show high expression of IL-3 receptor a chain in hematologic malignancies. Given the high frequency of CD123 reactivity in blast cells in contrast to in normal precursors, this antigen could be applied to the study of minimal residual disease in acute leukemia. CD123 is expressed with a characteristic pattern in cases of hairy cell leukemia.