Acute myelogenous leukemia (AML) occurs with increased frequency in patients or experimental animals exposed to x-rays or alkylating agents. To study the role of age and accumulated proliferative stress on the marrow pluripotent hemopoietic stem cell (PHSC) compartment in this process, marrow from weanling, young adult, or retired breeder mice of a low AML incidence strain (NIH/Swiss) and high incidence strain (Rfm) will be serially transferred to lethally irradiated syngeneic transplant recipients of a single age (4-6 months). Mice in each generation will be exposed to a leukemogenic dose or x-irradiation or nitrogen mustard and marrow explanted 3 weeks later to an in vitro culture system which maintains proliferation of PHSC (CFUs) and granulocyte-macrophage progenitor cells (CFUc) for 10 to 20 weeks. Weekly culture harvests will be tested in vitro for the number of leukemogenic clones generated. Methods will include: x-ray and drug treatment of mice, serial marrow transplant, long-term marrow cultures, sslony assays for CFUc, spleen colony assay for CFUs, establishment of leukemia cell lines and leukemogenicity tests of established cell lines in syngeneic newborn mice.