Both normal and leukemic cells proliferate clonally in a variety of semi-solid matrix cultures. Patterns of leukemic proliferation differ diagnostically from those of normals. Presently, growth patterns are identified in terms of numbers of cells capable of division and of the size attained by colonies within fixed time periods. We have developed techniques for sectioning agar matrix so that detailed microscopic examination of colonies in situ is possible. Peripheral maturation can be seen within individual clones derived from human marrow. We plan to identify and describe cells using histologic detail and developing histochemical, cytogenetic, and blood-group antigenic markers for cell type and maturation level. Such markers applied to leukemic cells should amplify the diagnostic value of clonal culture. We will use them to examine the question of whether sequences of maturing of a variety of cell functions are coordinated in leukemic cells as they are in their normal counterparts. Mouse models for granulocytic and lymphocytic leukemia will be utilized to determine correlations between clinical alterations in vivo and abnormal growth in vitro. Histochemical and antigenic markers for leukemic cells will be identified. Selected chemotherapeutic agents will be investigated for their ability to alter patterns of differentiation or cell growth in vitro.