Quantitative assays for individual hematopoietic progenitors have provided a powerful approach to the assessment of changes in the absolute and relative numbers of primitive cells in the affected tissues of individuals with CML. These techniques have also been usefully coupled to other ways of assessing these cells to confirm their malignant nature by cytogenetic analysis and to establish and characterize abnormalities in the regulation of their numbers and turnover. A culture system that allows primitive normal and leukemic hematopoiesis to be maintained for many weeks has been developed. This system has been found to reproduce the cardinal features of primitive hematopoietic cell regulation in vivo and its use has allowed important progress to be made in characterizing the molecular basis of stromal cell regulation of primitive hematopoietic cells. Nevertheless, a large gap still remains between our knowledge of the genes that are altered in CML (or other malignancies) and the biological changes underlying the deregulation of growth that is characteristic of malignancy in general. Further exploitation of in vitro systems that allow this deregulation to be analyzed and manipulated appears to offer promise towards bridging this gap in the future.