The OMA-AML-1, acute myelogenous leukemia cell line is unique in that it spontaneously maintains both a CD34+ precursor cell compartment and a CD15+ differentiating cell compartment in vitro. A third transitional cell type with co-expression of CD34 and CD15 can also be identified in in vitro cultures. The cell line shows dynamic fluctuations in the relative sizes of these three cell compartments in suspension culture. In contrast, OMA-AML-1 fails to show phenotypic or morphologic evidence of differentiation when grown subcutaneously in immunodeficient mice. OMA-AML-1 responds to a number of hematopoietic cytokines. Delineation of cytokine responses on FACS isolated populations of CD34+ versus CD15+ cells demonstrated that proliferative responses occurred primarily at the level of the precursor cell (CD34+) while the production of endstage eosinophils occurred within the CD15+ compartment. OMA-AML-1 mimics a number of features of normal hematopoiesis and is proving to be a useful in vitro model for the study of hematopoietic differentiation.